Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and wer...Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.展开更多
Cyclometallated platinum(Ⅱ)complexes,[(C^N^N)Pt^(Ⅱ)(L)]^(n+)(n=0 or 1),have attracted much attention due to their potency as luminescent probes for nucleic acids and anticancer agents.Reported herein are four[(C^N^N...Cyclometallated platinum(Ⅱ)complexes,[(C^N^N)Pt^(Ⅱ)(L)]^(n+)(n=0 or 1),have attracted much attention due to their potency as luminescent probes for nucleic acids and anticancer agents.Reported herein are four[(C^N^N)Pt^(Ⅱ)(L)]^(+)complexes(5-8,L=4-anilinoquinazoline derivative)which exhibit a weak fluorescence emission over 605 to 627 nm upon excitation at 405 nm.The ligation of the cyclometallated platinum cores with EGFR-inhibiting anilinoquinazolines not only confers the resulting complexes with excellent EGFR-inhibiting potency with IC_(50)values at the nanomolar level.展开更多
Correction for‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent’by Matteo Fiaschi et al.,Inorg.Chem.Front.,2024,11,2841-2...Correction for‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent’by Matteo Fiaschi et al.,Inorg.Chem.Front.,2024,11,2841-2862,https://doi.org/10.1039/D4QI00096J.展开更多
We conducted a systematic study on the reactivity of[Ru_(2)Cp_(2)(CO)4](Cp=η^(5)-C_(5)H_(5))with isocyanides and the subsequent methylation reaction to produce[Ru_(2)Cp_(2)(CO)2(μ-CO){μ-CNMe(R)}]^(+)complexes as CF...We conducted a systematic study on the reactivity of[Ru_(2)Cp_(2)(CO)4](Cp=η^(5)-C_(5)H_(5))with isocyanides and the subsequent methylation reaction to produce[Ru_(2)Cp_(2)(CO)2(μ-CO){μ-CNMe(R)}]^(+)complexes as CF_(3)SO_(3)^(−)salts,[2a-h]^(+)[R=Me,cyclohexyl(Cy),2,6-C_(6)H_(3)Me_(2)(Xyl),1H-indol-5-yl,2-naphthyl,4-C_(6)H_(4)OMe,(S)-CHMe(Ph),CH_(2)Ph(Bn)].The resulting products,including five novel ones,underwent structural characterization by IR and multinuclear NMR spectroscopy,with five of them further confirmed via single crystal X-ray diffraction.Compounds[2a-e,h]CF_(3)SO_(3)exhibit appreciable water solubility,substantial amphiphilic character and out-standing stability in physiological-like solutions(negligible degradation after 72 hours in DMEM at 37℃).Representative complexes[2b]^(+)and[2c]^(+)were additionally characterized through cyclic voltammetry in CH_(2)Cl_(2)and in aqueous phosphate buffer solution.Compounds[2a-d]CF_(3)SO_(3)were assessed for in vitro cyto-toxicity against A2780,A2080R and MCF-7 human cancer cell lines,and[2a-c]CF_(3)SO_(3)revealed significant-to-moderate cytotoxicity,outperforming cisplatin in several cases.The most favourable IC_(50)values were observed for[2d]CF_(3)SO_(3),ranging from 3.7 to 13.0μM.Experiments on the noncancerous human cell line MRC-5 highlighted a reasonable selectivity for[2b-d]CF_(3)SO_(3),with the highest selectivity indexes(SI)calcu-lated as 10.1(ratio of IC_(50)on MRC-5/IC_(50)on A2780)and 8.5(ratio of IC_(50)on MRC-5/IC_(50)on A2780R)for[2d]CF_(3)SO_(3).Subsequently,[2d]CF_(3)SO_(3)was tested across a panel of HOS,A549,PANC1,CaCo2,PC3 and HeLa cancer cells,showing variable cytotoxicity with IC_(50)values in the range of 9.7 to 20.3μM.The cellular effects of[2d]^(+)on A2780 cells were investigated using flow cytometry assays,focusing on the cell cycle modification,time-resolved cellular uptake,intracellular ROS production,mitochondrial membrane depolarization,induction of cell death through apoptosis,activation of caspases 3/7 and induction of autophagy.Overall,the results suggest a diphasic mechanism of action for[2d]^(+),inducing metabolic stress and arresting proliferation in the first/fast phase,followed by the induction of apoptosis and autophagy in the second/slower phase.展开更多
A series of coordination gold(Ⅲ),palladium(Ⅱ),and platinum(Ⅱ)complexes with a luminescent iminophosphorane ligand derived from 8-aminoquinoline[Ph_(3)PvN-C_(9)H_(6)N](1)have been synthesized and structurally charac...A series of coordination gold(Ⅲ),palladium(Ⅱ),and platinum(Ⅱ)complexes with a luminescent iminophosphorane ligand derived from 8-aminoquinoline[Ph_(3)PvN-C_(9)H_(6)N](1)have been synthesized and structurally characterized.The coordination palladium(Ⅱ)and platinum(Ⅱ)compounds can evolve further,under appropriate conditions,to give stable cyclometalated endo species[M{κ_(3)-C,N,N-C_(6)H_(4)(PPh_(2)vN-8-C_(9)H_(6)N)}Cl](M=Pd,Pt)by C-H activation of the phenyl group of the PPh_(3)fragment.展开更多
This study aimed to design novel 1,8-naphthyridine derivatives as potential anticancer agents that target topoisomerase Ⅱ via a ligand-based drug design strategy.We developed a robust quantitative structure-activity ...This study aimed to design novel 1,8-naphthyridine derivatives as potential anticancer agents that target topoisomerase Ⅱ via a ligand-based drug design strategy.We developed a robust quantitative structure-activity relationship model via multiple linear regression,achieving a coefficient of determination(R 2)of 0.6991.External validation demonstrated high predictive ability,with Q^(2)(F1)and Q^(2)(F2)scores of 0.8683 and 0.8670,respectively,indicating substantial reliability in predicting the biological activity of new compounds.Our dataset includes 23 analogs of 1,8-naphthyridine derivatives.The 2-dimensional structures of these compounds were drawn via ChemDraw 15.0 and optimized via density functional theory with the B3LYP hybrid functional approach via Spartan 14.1.Molecular descriptors were calculated via PaDEL software and further processed via Data Pretreatment Software V.WPS 1.2.The Kennard-Stone algorithm in the dataset division graphical user interface 1.2 split the dataset into training and test sets.Docking studies against the DNA topoisomerase Ⅱ receptor(Protein Data Bank ID:1ZXM)revealed substantial interactions,with all the newly designed ligands(L1 to L5)exhibiting superior binding affinities(-9.3 to-8.9 kcal/mol)compared with the existing datasets and the standard drug bevacizumab(-6.0 kcal/mol).The pharmacokinetic evaluation revealed zero violations of Lipinski’s rule of five.Hence,further in-depth in vitro and in vivo investigations are recommended to validate these theoretical findings.展开更多
In 1979,the mechanism of chemical carcinogenesis,a challenging anddifficult scientific problem pending for a number of years,was explained by Dai Qianhuan.Themechanism named di-region theory predicted that a carcinoge...In 1979,the mechanism of chemical carcinogenesis,a challenging anddifficult scientific problem pending for a number of years,was explained by Dai Qianhuan.Themechanism named di-region theory predicted that a carcinogen always metabolizes to form a specialbi-functional alky-lating agent.This agent induces cross-linkages between the complementary basepairs in DMA and switches on initial mutageneses in genomes including point and frameshiftmutations.This,in turn,induces further deep mutageneses including the production of variouschimeric chromosomes,deletions and other aberrations found in genomes.In the end this initiatescarcinogenesis of the whole cell through the reverse transcription mechanism after a lengthyincubation period.Recently,this laboratory has verified that physical carcinogenesis,includingthe oncogenesis induced by radiation and asbestos as well as the carcinogenesis induced byendogenous factors such as estrogen or diethyl-stilbestrol switch on carcinogenesis by inducing theformation of cross-linkages between the complementary base pairs in DNA.Di-region theory has nowbeen supported by many experimental observations such as mutational spectra of various carcinogens.The potential for carcinogenesis,teratogenesis,sterility and mutagenesis lumped together asgenetic toxicity appears to originate almost uniformly from the cross-linking between complementarybases,i.e.malignant cross-linking,which is in accordance with di-region theory.Other forms ofcross-linking between non-complementary bases,benign cross-linkings,show bi-functional alkylationanticancer activity but lack genetic toxicity.The predictable design and synthesis of a highselectivity anticancer agent with high efficacy and low genetic toxicity,a goal long pursued incancer chemotherapy,have been realized for the first time in this laboratory by inhibitingmalignant and heightening benign cross-linking using the principles of di-region theory.A series ofpatented new anticancer platinum complexes called di-regioplatins,based on the above predetermineddesign,have been reported.In these cancer cell kill rates,tumor-inhibition rates and theultimate life-span for two mouse carcinoma models using several compounds ofcis-di-substituted-benzylaminodihaloplatinum(II)are notably higher than those of cisplatin,buttheir toxicities all are much lower than cisplatin.Based on a predictive design using di-regiontheory and group theory,a new anticancer complex,cis-diammine-cyclopentane-1,1-dicarboxylato-platinum(II)called minoplatin,has been synthesized inthis laboratory by making the minimal structural revision of adding an CH_2 unit on the four-memberring of carboplatin.展开更多
RNA plays important roles as a gene-silencing agent, a therapeutic agent for clinical treatment, and in the differentiation, proliferation, and development of cells. However, RNA is very difficult to work with due to ...RNA plays important roles as a gene-silencing agent, a therapeutic agent for clinical treatment, and in the differentiation, proliferation, and development of cells. However, RNA is very difficult to work with due to its sensitivity and fragility. Another obstacle in using RNA for gene delivery/silencing is its negative charge, which causes its repulsion by cell membranes, which are also negatively charged. Our recent study showed that miR-125b is upregulated in glioblastoma （GMB） and plays an oncogenic role in GMB cells by promoting cell proliferation and inhibiting apoptosis. Endogenous miR-125b can be blocked by transfection of its antisense RNA molecule, miR-125b antisense （miR-125b-AS）. Thus, miR- 125b-AS can be developed as an RNA-based agent for cancer treatment. However, instability during storage and difficulty in delivery into cells has limited the use of RNA-based therapies thus far. In the current work, we demonstrate a short and simple one-step technique for the preparation of positively charged RNA nanospheres （miR-125b-RNS and miR-125b-AS-RNS） coated with a bioavailable polymer, polyethylenimine （PEI）. These RNA nanospheres are able to penetrate the cell directly without the use of liposomes. Our study confirmed that converting miR-125b and miR-125b-AS into nanospheres is a viable approach for storing RNA. In addition, this study provides evidence that PEI-coated RNA nanospheres have the potential to be used as a novel class of anticancer a^ents.展开更多
A novel hetero-bimetallic transition metal(Sb^(Ⅴ)/Mn^(Ⅱ))-substituted Krebs-type polyoxometalate(POM)with N-chelating ligand H_(4)Na_(4)[Mn_(4)(H_(2)O)_(4)(trz)_(2)(SbO_(2))_(2)(SbW_(9)O_(33))_(2)]-20H_(2)O(Sb_(2)Mn...A novel hetero-bimetallic transition metal(Sb^(Ⅴ)/Mn^(Ⅱ))-substituted Krebs-type polyoxometalate(POM)with N-chelating ligand H_(4)Na_(4)[Mn_(4)(H_(2)O)_(4)(trz)_(2)(SbO_(2))_(2)(SbW_(9)O_(33))_(2)]-20H_(2)O(Sb_(2)Mn_(2))(1)(trz=1,2,4-triazole)built from trilacunary Keggin POM unitα-B-[SbW_(9)O_(33)]^(9-){SbW_(9)]has been synthesized and characterized by single-crystal/powder X-ray diffraction and a wide range of analytical methods,including powder X-ray diffraction,Fourier transform infrared spectroscopy,Raman,ultraviolet-visible spectroscopy,electrospray ionization-mass spectroscopy,and thermogravimetric analysis.To further investigate the antitumor activity of the(Sb_(2)Mn_(2))(1)in human gastric cancer Human Gastric Adenocarcinoma Cells and Human Gastric Cancer Cell lines,in vitro cytotoxicity assay and flow cytometry analysis was performed.The results indicated that the IC_(50) values of(Sb_(2)Mn_(2))(1)on Human Gastric Adenocarcinoma(AGS)and Human Gastric Cancer(BGC-823)Cell Lines were 1.86±0.05μmol·L^(-1) and 14.61±0.55μmol·L^(-1),respectively.(Sb_(2)Mn_(2))(1)also exhibited high cytotoxicity on Human Gastric Cancer Cells and could induce cell apoptosis by inhibiting S and G_(2)/M cell cycles.Therefore,the result not only shows that this new POM-based inorganic-organic hybrid compound has high selectivity and low toxicity,but also provides an effective method for the development of potential transition metal-substituted POMs based antitumor drugs.展开更多
Alkylating agents represent an important class of anticancer drugs.The occurrence and emergence of tumor resistance to the treatment with alkylating agents denotes a severe problem in the clinics.A detailed understand...Alkylating agents represent an important class of anticancer drugs.The occurrence and emergence of tumor resistance to the treatment with alkylating agents denotes a severe problem in the clinics.A detailed understanding of the mechanisms of activity of alkylating drugs is essential in order to overcome drug resistance.In particular,the role of non-coding microRNAs concerning alkylating drug activity and resistance in various cancers is highlighted in this review.Both synthetic and natural alkylating agents,which are approved for cancer therapy,are discussed concerning their interplay with microRNAs.展开更多
The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven huma...The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1 - 4, 6 - 8 and compounds 10 and 11) showed promising anticancer activities with IC<sub>50</sub>s ranging from 0.83 to 2.58 μM. Compounds 2 and 6 with IC<sub>50</sub>s of 0.83 and 0.86 μM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (E<sub>elec</sub>), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.展开更多
Chemotherapy is still the effective strategy for treating cancer.It is important to explore anticancer agents from Traditional Chinese Medicine and Natural products.Different cancer cell lines were included in our res...Chemotherapy is still the effective strategy for treating cancer.It is important to explore anticancer agents from Traditional Chinese Medicine and Natural products.Different cancer cell lines were included in our research,such as HL60,K562,K562/ADR,KB,KBv200 cells.Cell growth inhibition assay,Annexin V-FITC/PI double-staining assay,measurement of reactive展开更多
AIM： To evaluate the anticancer property of the dried latex （DL） of Calotropis procera, a tropical medicinal plant, in the X15-myc transgenic mouse model of hepatocellular carcinoma and to elucidate its mechanism o...AIM： To evaluate the anticancer property of the dried latex （DL） of Calotropis procera, a tropical medicinal plant, in the X15-myc transgenic mouse model of hepatocellular carcinoma and to elucidate its mechanism of action in cell culture. METHODS： The young transgenic mice were orally fed with the aqueous suspension of DL （400 mg/kg for 5 d/wk） for 15 wk and their liver was examined for histopathological changes at 20 wk. Serum levels of vascu- lar endothelial growth factor （VEGF） were also measured in these animals. To characterize the active fraction, DL was extracted with petroleum ether followed by methanol. The methanolic extract was sub-fractionated on a silica gel G column using a combination of non-polar and polar solvents and eleven fractions were obtained. Each fraction was analysed for cytotoxic effect on hepatoma （Huh7） and non-hepatoma （COS-1） cell lines and nontransformed hepatocytes （AML12） using tetrazolium （MTT） assay. Finally, the mechanism of cell death was investigated by measuring the levels of Bcl2, caspase 3 and DNA fragmentation. RESULTS： DL treatment of mice showed a complete protection against hepatocarcinogenesis. No adverse effect was observed in these animals. The serum VEGF level was significantly lowered in the treated mice as compared to control animals. Cell culture studies revealed that the methanolic extract of DL as well as its fraction 8 induced extensive cell death in both Huh-7 and COS-1 cells while AML12 cells were spared. This was accompanied by extensive fragmentation of DNA in Huh-7 and COS-1 cells. No change in the levels of canonical markers of apoptosis such as Bcl2 and caspase 3 was observed. CONCLUSION： DL of C. procera has the potential for anti-cancer therapy due to its differentJable targets and non-interference with regular pathway of apoptosis.展开更多
Plant natural products including alkaloids,polyphenols,terpenoids and flavonoids have been reported to exert anticancer activity by targeting various metabolic pathways.The biological pathways regulated by plant produ...Plant natural products including alkaloids,polyphenols,terpenoids and flavonoids have been reported to exert anticancer activity by targeting various metabolic pathways.The biological pathways regulated by plant products can serve as novel drug targets.Plant natural compounds or their derivatives used for cancer treatment and some novel plant-based compounds which are used in clinical trials were discussed.Callus suspension culture with secondary metabolites can provide a continuous source of plant pharmaceuticals without time and space limitations.Previous research has shown that rice callus suspension culture can kill>95%cancer cells with no significant effect on the growth of normal cells.The role of candidate genes and metabolites which are likely to be involved in the process and their potential to serve as anticancer and anti-inflammatory agents were discussed.Large scale production of plant callus suspension culture and its constituents can be achieved using elicitors which enhance specific secondary metabolites combined with bioprocess technology.展开更多
Herein,a new class of iridium(Ⅲ)-based metal complexes with phosphine-imine(P^N)ligands are synthesized and authenticated.These complexes show high cytotoxicities against seven cancer cells in vitro.Simultaneously,an...Herein,a new class of iridium(Ⅲ)-based metal complexes with phosphine-imine(P^N)ligands are synthesized and authenticated.These complexes show high cytotoxicities against seven cancer cells in vitro.Simultaneously,antitumor mechanism studies show that complex Ir3 induces apoptosis by depolarization of mitochondrial membrane potential,ROS overproduction and ROS-mediated DNA damage.Importantly,BIX01294,a G9a histone methyltransferase inhibitor,could markedly sensitize Ir3-induced cytotoxicity,cell cycle arrest,apoptosis and inhibition of migration in HCT116 cancer cells in vitro.Finally,we show that combined treatment with Ir3 and BIX01294 potently inhibits tumour growth and lung metastasis in vivo.Taken together,we demonstrate that BIX01294 could potently sensitize iridium(Ⅲ)-based metal complex-induced inhibition of tumour progression and provide the basis for developing new metal-based anticancer agents and therapeutic strategies in vivo for effective cancer therapy.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
Aziridine and its N-substituted derivatives could undergo nucleophilic ring opening reaction with biological molecules, leading to their alkylation and the loss of their biological activities. For this purpose, ethyl ...Aziridine and its N-substituted derivatives could undergo nucleophilic ring opening reaction with biological molecules, leading to their alkylation and the loss of their biological activities. For this purpose, ethyl 4-[N-methyl-N-（2,3-aziridinyl）amino] benzoate and diethyl N-{4-[N-methyl-N-（2,3-aziridinyl）amino]benzoyl}-L-glutamate, as the key intermediates in the synthesis of new anticancer agents, were designed and synthesized via four steps of reactions in good yields.展开更多
Breast cancer is the most common cancer among women globally,where advancements in screening and treatment have significantly raised survival rates.The present investigation aims to identify the bioactive metabolites ...Breast cancer is the most common cancer among women globally,where advancements in screening and treatment have significantly raised survival rates.The present investigation aims to identify the bioactive metabolites from Thalassia hemprichii and elucidate their mechanism through an integrated in vitro and in silico molecular docking approach.The crude extract has 27.2 mg GAE/g and 23.9 QE/g of phenolic and flavonoid content as revealed by preliminary phytochemical screening,which signifies and contributes better antioxidant properties.The anticancer assays demonstrated a significant reduction in the viability of breast cancer cell lines(MCF-7),with IC_(50) values(35.86μg/ml)indicating anticancer property.Mass spectroscopy data indicate the presence of 11 compounds,and these identified compounds demonstrate promising absorption and bioavailability scores based on Lipinski’s rules.Molecular docking studies suggested the high binding affinity of Betulin with key cancer-related proteins(e.g.,-9.28 kcal/mol with STAT3),highlighting its potential as a lead compound in breast cancer drug development.The pharmacological network is moderately significant and interacts with target proteins STAT3,SRC,EGFR,ESR1,HSP90AA1,HSP90AB2,PTGS2,GSK3B,MMP9,and CCND1.This research emphasizes the network pharmacology with in silico docking and in vitro assay validation to facilitate a comprehensive perspective of T.hemprichii extract against breast cancer with compound-target-pathway interrelations,indicating T.hemprichii as a possible multitargeting drug for breast cancer.Although these results show promise for seagrass as a potential therapeutic nutraceutical,further in vivo studies are important to understand the underlying molecular mechanisms in human metabolism.展开更多
Mono-axial functionalised octahedral diazido Pt(IV)complexes trans,trans,trans-[Pt(py)_(2)(N_(3))_(2)(OR_(1))(OR_(2))](OR_(1)=OH and OR_(2)=anticancer agent coumarin-3 carboxylate(cou,2a),pyruvate dehydrogenase kinase...Mono-axial functionalised octahedral diazido Pt(IV)complexes trans,trans,trans-[Pt(py)_(2)(N_(3))_(2)(OR_(1))(OR_(2))](OR_(1)=OH and OR_(2)=anticancer agent coumarin-3 carboxylate(cou,2a),pyruvate dehydrogenase kinase(PDK)inhibitors 4-phenylbutyrate(PhB,2b)or dichloroacetate(DCA,2c)),and their di-axial functionalised analogues with OR_(1)=DCA and OR_(2)=cou(3a),PhB(3b),or DCA(3c)have been synthesised and characterised,including the X-ray crystal structures of complexes 2a,3a,3b and 3c.These complexes exhibit dark stability and have the potential to generate cytotoxic Pt(II)species and free radicals selectively in cancer cells when irradiated.Mono-functionalised complexes 2a-2c showed higher aqueous solubility and more negative reduction potentials.Mono-and di-functionalised complexes displayed higher photocytotoxicity with blue light(1 h,465 nm,4.8 mW cm^(-2))than the parent dihydroxido complex 1(OR_(1)=OR_(2)=OH)in A2780 human ovarian(IC_(50)0.9-2.9μM for 2a-2c;0.11-0.39μM for 3a-3c)and A549 human lung cancer cells(5.4-7.8μM for 2a-2c;1.2-2.6μM for 3a-3c)with satisfactory dark stability.Notably,no apparent dark cytotoxicity was observed in healthy lung MRC-5 fibroblasts for all complexes(IC_(50)>20μM).Significantly higher platinum cellular accumulation and photo-generated ROS levels were observed for the di-functionalised complexes compared with their mono-functionalised analogues when cancer cells were treated under the same concentrations.展开更多
Transition metal complexes with substituted high affinity mixed ligands as potential anticancer agents can overcome the drawbacks of platinum-based drugs that are currently being marketed.Here,a new watersoluble asymm...Transition metal complexes with substituted high affinity mixed ligands as potential anticancer agents can overcome the drawbacks of platinum-based drugs that are currently being marketed.Here,a new watersoluble asymmetric binuclear iminodiacetato-zinc(II)complex[Zn_(2)(ida)(phen)_(3)(NO_(3))]·NO_(3)·5H_(2)O(1)with a phenanthroline ligand has been synthesized and fully characterized with a wide range of analytical techniques including single crystal X-ray diffraction as well as spectroscopic techniques,such as FT-IR,UV/Vis,photoluminescence spectroscopy,and furthermore by elemental and thermogravimetric analyses.Moreover,unprecedented(H_(2)O)_(10)water clusters consisting of a quasi-planar tetramer and six dangling water molecules were observed in the void space of 3D supramolecular assemblies.The conversion behavior of(1)into two monomeric species[Zn(ida)(phen)(H_(2)O)](2)and[Zn(phen)_(2)(H_(2)O)_(2)]^(2+)(3)in aqueous solution was first studied by solid-state/solution NMR,ESI-MS,and solution UV/vis spectra.Next,these zinc(II)complexes(1-3),a mixture of(2)and(3)(mole ratio 1/1),ligands(phen and ida)and zinc ions(ZnCl_(2)and ZnSO_(4))were further evaluated for the in vitro cytotoxic profile in human hepatoma cell lines(HepG2 and SMMC-7721).We found that complex(1)effectively inhibited the proliferation of hepatocellular carcinoma cells,which is similar to a mixture of(2)and(3)in a 1:1 molar ratio,and IC50 values of(1)were almost about 20-50%of(2)or(3).Therefore,this binuclear complex(1)mainly acts as a cooperative inhibitor with complexes(2)and(3)toward tumor growth in solution.We further extended the preliminary research of complex(1)and found that(1)could induce cell cycle arrest at the G0/G1 phase.Additionally,overdosing on(1)exhibited low toxicity of mice(LD_(50)of(1)in ICR mice=736 mg kg^(-1),with 95%confidence interval 635-842 mg kg^(-1)).In conclusion,complex(1)with a high antitumor activity and low toxicity provides a new strategy for the treatment of liver cancer.展开更多
文摘Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.
基金NSFC(Grant No.21135006,21127901,21575145 and 21621062)the 973 Program of MOST(2013CB531805)for supportProf.Dihua Shangguan and Dr Tao Bing at the Institute of Chemistry,Chinese Academy of Sciences for the gift of the Pu27 quadruplex DNA and BPBC fluorescence probe.
文摘Cyclometallated platinum(Ⅱ)complexes,[(C^N^N)Pt^(Ⅱ)(L)]^(n+)(n=0 or 1),have attracted much attention due to their potency as luminescent probes for nucleic acids and anticancer agents.Reported herein are four[(C^N^N)Pt^(Ⅱ)(L)]^(+)complexes(5-8,L=4-anilinoquinazoline derivative)which exhibit a weak fluorescence emission over 605 to 627 nm upon excitation at 405 nm.The ligation of the cyclometallated platinum cores with EGFR-inhibiting anilinoquinazolines not only confers the resulting complexes with excellent EGFR-inhibiting potency with IC_(50)values at the nanomolar level.
文摘Correction for‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent’by Matteo Fiaschi et al.,Inorg.Chem.Front.,2024,11,2841-2862,https://doi.org/10.1039/D4QI00096J.
基金L.B.,T.F.and F.M.thank the University of Pisa(Fondi di Ateneo 2020 and PRA_2020_39)for financial supportJ.V.,T.M.and Z.T.acknowledge the financial support from the ERDF/ESF Project Nanotechnologies for Future(CZ.02.1.01/0.0/0.0/16_019/0000754)thank Ms Marta Rešováfor help with biological testing,Prof.MarekŠebela for assistance with MALDI-TOF MS experiments,and Dr Ondřej Vrobel for assist-ance with some of the mass spectrometry experiments。
文摘We conducted a systematic study on the reactivity of[Ru_(2)Cp_(2)(CO)4](Cp=η^(5)-C_(5)H_(5))with isocyanides and the subsequent methylation reaction to produce[Ru_(2)Cp_(2)(CO)2(μ-CO){μ-CNMe(R)}]^(+)complexes as CF_(3)SO_(3)^(−)salts,[2a-h]^(+)[R=Me,cyclohexyl(Cy),2,6-C_(6)H_(3)Me_(2)(Xyl),1H-indol-5-yl,2-naphthyl,4-C_(6)H_(4)OMe,(S)-CHMe(Ph),CH_(2)Ph(Bn)].The resulting products,including five novel ones,underwent structural characterization by IR and multinuclear NMR spectroscopy,with five of them further confirmed via single crystal X-ray diffraction.Compounds[2a-e,h]CF_(3)SO_(3)exhibit appreciable water solubility,substantial amphiphilic character and out-standing stability in physiological-like solutions(negligible degradation after 72 hours in DMEM at 37℃).Representative complexes[2b]^(+)and[2c]^(+)were additionally characterized through cyclic voltammetry in CH_(2)Cl_(2)and in aqueous phosphate buffer solution.Compounds[2a-d]CF_(3)SO_(3)were assessed for in vitro cyto-toxicity against A2780,A2080R and MCF-7 human cancer cell lines,and[2a-c]CF_(3)SO_(3)revealed significant-to-moderate cytotoxicity,outperforming cisplatin in several cases.The most favourable IC_(50)values were observed for[2d]CF_(3)SO_(3),ranging from 3.7 to 13.0μM.Experiments on the noncancerous human cell line MRC-5 highlighted a reasonable selectivity for[2b-d]CF_(3)SO_(3),with the highest selectivity indexes(SI)calcu-lated as 10.1(ratio of IC_(50)on MRC-5/IC_(50)on A2780)and 8.5(ratio of IC_(50)on MRC-5/IC_(50)on A2780R)for[2d]CF_(3)SO_(3).Subsequently,[2d]CF_(3)SO_(3)was tested across a panel of HOS,A549,PANC1,CaCo2,PC3 and HeLa cancer cells,showing variable cytotoxicity with IC_(50)values in the range of 9.7 to 20.3μM.The cellular effects of[2d]^(+)on A2780 cells were investigated using flow cytometry assays,focusing on the cell cycle modification,time-resolved cellular uptake,intracellular ROS production,mitochondrial membrane depolarization,induction of cell death through apoptosis,activation of caspases 3/7 and induction of autophagy.Overall,the results suggest a diphasic mechanism of action for[2d]^(+),inducing metabolic stress and arresting proliferation in the first/fast phase,followed by the induction of apoptosis and autophagy in the second/slower phase.
基金Research at Brooklyn College was supported by a grant from the National Institute of General Medical Sciences(NIGMS),SC2GM082307a grant from the National Cancer Institute(NCI),1SC1CA182844(M.C.)+1 种基金the MINECO“Ministerio de Ciencia y Economía”(CTQ2011-22589)Gobierno de Aragón(Dpto.de Ciencia,Tecnología y Universidad)for financial support(J.J.).
文摘A series of coordination gold(Ⅲ),palladium(Ⅱ),and platinum(Ⅱ)complexes with a luminescent iminophosphorane ligand derived from 8-aminoquinoline[Ph_(3)PvN-C_(9)H_(6)N](1)have been synthesized and structurally characterized.The coordination palladium(Ⅱ)and platinum(Ⅱ)compounds can evolve further,under appropriate conditions,to give stable cyclometalated endo species[M{κ_(3)-C,N,N-C_(6)H_(4)(PPh_(2)vN-8-C_(9)H_(6)N)}Cl](M=Pd,Pt)by C-H activation of the phenyl group of the PPh_(3)fragment.
文摘This study aimed to design novel 1,8-naphthyridine derivatives as potential anticancer agents that target topoisomerase Ⅱ via a ligand-based drug design strategy.We developed a robust quantitative structure-activity relationship model via multiple linear regression,achieving a coefficient of determination(R 2)of 0.6991.External validation demonstrated high predictive ability,with Q^(2)(F1)and Q^(2)(F2)scores of 0.8683 and 0.8670,respectively,indicating substantial reliability in predicting the biological activity of new compounds.Our dataset includes 23 analogs of 1,8-naphthyridine derivatives.The 2-dimensional structures of these compounds were drawn via ChemDraw 15.0 and optimized via density functional theory with the B3LYP hybrid functional approach via Spartan 14.1.Molecular descriptors were calculated via PaDEL software and further processed via Data Pretreatment Software V.WPS 1.2.The Kennard-Stone algorithm in the dataset division graphical user interface 1.2 split the dataset into training and test sets.Docking studies against the DNA topoisomerase Ⅱ receptor(Protein Data Bank ID:1ZXM)revealed substantial interactions,with all the newly designed ligands(L1 to L5)exhibiting superior binding affinities(-9.3 to-8.9 kcal/mol)compared with the existing datasets and the standard drug bevacizumab(-6.0 kcal/mol).The pharmacokinetic evaluation revealed zero violations of Lipinski’s rule of five.Hence,further in-depth in vitro and in vivo investigations are recommended to validate these theoretical findings.
文摘In 1979,the mechanism of chemical carcinogenesis,a challenging anddifficult scientific problem pending for a number of years,was explained by Dai Qianhuan.Themechanism named di-region theory predicted that a carcinogen always metabolizes to form a specialbi-functional alky-lating agent.This agent induces cross-linkages between the complementary basepairs in DMA and switches on initial mutageneses in genomes including point and frameshiftmutations.This,in turn,induces further deep mutageneses including the production of variouschimeric chromosomes,deletions and other aberrations found in genomes.In the end this initiatescarcinogenesis of the whole cell through the reverse transcription mechanism after a lengthyincubation period.Recently,this laboratory has verified that physical carcinogenesis,includingthe oncogenesis induced by radiation and asbestos as well as the carcinogenesis induced byendogenous factors such as estrogen or diethyl-stilbestrol switch on carcinogenesis by inducing theformation of cross-linkages between the complementary base pairs in DNA.Di-region theory has nowbeen supported by many experimental observations such as mutational spectra of various carcinogens.The potential for carcinogenesis,teratogenesis,sterility and mutagenesis lumped together asgenetic toxicity appears to originate almost uniformly from the cross-linking between complementarybases,i.e.malignant cross-linking,which is in accordance with di-region theory.Other forms ofcross-linking between non-complementary bases,benign cross-linkings,show bi-functional alkylationanticancer activity but lack genetic toxicity.The predictable design and synthesis of a highselectivity anticancer agent with high efficacy and low genetic toxicity,a goal long pursued incancer chemotherapy,have been realized for the first time in this laboratory by inhibitingmalignant and heightening benign cross-linking using the principles of di-region theory.A series ofpatented new anticancer platinum complexes called di-regioplatins,based on the above predetermineddesign,have been reported.In these cancer cell kill rates,tumor-inhibition rates and theultimate life-span for two mouse carcinoma models using several compounds ofcis-di-substituted-benzylaminodihaloplatinum(II)are notably higher than those of cisplatin,buttheir toxicities all are much lower than cisplatin.Based on a predictive design using di-regiontheory and group theory,a new anticancer complex,cis-diammine-cyclopentane-1,1-dicarboxylato-platinum(II)called minoplatin,has been synthesized inthis laboratory by making the minimal structural revision of adding an CH_2 unit on the four-memberring of carboplatin.
文摘RNA plays important roles as a gene-silencing agent, a therapeutic agent for clinical treatment, and in the differentiation, proliferation, and development of cells. However, RNA is very difficult to work with due to its sensitivity and fragility. Another obstacle in using RNA for gene delivery/silencing is its negative charge, which causes its repulsion by cell membranes, which are also negatively charged. Our recent study showed that miR-125b is upregulated in glioblastoma （GMB） and plays an oncogenic role in GMB cells by promoting cell proliferation and inhibiting apoptosis. Endogenous miR-125b can be blocked by transfection of its antisense RNA molecule, miR-125b antisense （miR-125b-AS）. Thus, miR- 125b-AS can be developed as an RNA-based agent for cancer treatment. However, instability during storage and difficulty in delivery into cells has limited the use of RNA-based therapies thus far. In the current work, we demonstrate a short and simple one-step technique for the preparation of positively charged RNA nanospheres （miR-125b-RNS and miR-125b-AS-RNS） coated with a bioavailable polymer, polyethylenimine （PEI）. These RNA nanospheres are able to penetrate the cell directly without the use of liposomes. Our study confirmed that converting miR-125b and miR-125b-AS into nanospheres is a viable approach for storing RNA. In addition, this study provides evidence that PEI-coated RNA nanospheres have the potential to be used as a novel class of anticancer a^ents.
基金This work was supported by the National Natural Science Foundation of China(No.21971221,21401162)the Yangzhou University Interdisciplinary Research Foundation for Chemistry Discipline(yzuxk202010)+2 种基金Qing Lan Project in Colleges and Universities of Jiangsu ProvinceInnovation and entrepreneurship training programs for college students in Jiangsu(202211117066Z)Y.Zhang acknowledges supports from Guangxi Natural Science Foundation(AD20238043,2018GXNSFDA281002)。
文摘A novel hetero-bimetallic transition metal(Sb^(Ⅴ)/Mn^(Ⅱ))-substituted Krebs-type polyoxometalate(POM)with N-chelating ligand H_(4)Na_(4)[Mn_(4)(H_(2)O)_(4)(trz)_(2)(SbO_(2))_(2)(SbW_(9)O_(33))_(2)]-20H_(2)O(Sb_(2)Mn_(2))(1)(trz=1,2,4-triazole)built from trilacunary Keggin POM unitα-B-[SbW_(9)O_(33)]^(9-){SbW_(9)]has been synthesized and characterized by single-crystal/powder X-ray diffraction and a wide range of analytical methods,including powder X-ray diffraction,Fourier transform infrared spectroscopy,Raman,ultraviolet-visible spectroscopy,electrospray ionization-mass spectroscopy,and thermogravimetric analysis.To further investigate the antitumor activity of the(Sb_(2)Mn_(2))(1)in human gastric cancer Human Gastric Adenocarcinoma Cells and Human Gastric Cancer Cell lines,in vitro cytotoxicity assay and flow cytometry analysis was performed.The results indicated that the IC_(50) values of(Sb_(2)Mn_(2))(1)on Human Gastric Adenocarcinoma(AGS)and Human Gastric Cancer(BGC-823)Cell Lines were 1.86±0.05μmol·L^(-1) and 14.61±0.55μmol·L^(-1),respectively.(Sb_(2)Mn_(2))(1)also exhibited high cytotoxicity on Human Gastric Cancer Cells and could induce cell apoptosis by inhibiting S and G_(2)/M cell cycles.Therefore,the result not only shows that this new POM-based inorganic-organic hybrid compound has high selectivity and low toxicity,but also provides an effective method for the development of potential transition metal-substituted POMs based antitumor drugs.
文摘Alkylating agents represent an important class of anticancer drugs.The occurrence and emergence of tumor resistance to the treatment with alkylating agents denotes a severe problem in the clinics.A detailed understanding of the mechanisms of activity of alkylating drugs is essential in order to overcome drug resistance.In particular,the role of non-coding microRNAs concerning alkylating drug activity and resistance in various cancers is highlighted in this review.Both synthetic and natural alkylating agents,which are approved for cancer therapy,are discussed concerning their interplay with microRNAs.
文摘The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1 - 4, 6 - 8 and compounds 10 and 11) showed promising anticancer activities with IC<sub>50</sub>s ranging from 0.83 to 2.58 μM. Compounds 2 and 6 with IC<sub>50</sub>s of 0.83 and 0.86 μM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (E<sub>elec</sub>), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.
文摘Chemotherapy is still the effective strategy for treating cancer.It is important to explore anticancer agents from Traditional Chinese Medicine and Natural products.Different cancer cell lines were included in our research,such as HL60,K562,K562/ADR,KB,KBv200 cells.Cell growth inhibition assay,Annexin V-FITC/PI double-staining assay,measurement of reactive
基金Supported by the core grant of International Centre for Genetic Engineering and Biotechnology. New Delhi
文摘AIM： To evaluate the anticancer property of the dried latex （DL） of Calotropis procera, a tropical medicinal plant, in the X15-myc transgenic mouse model of hepatocellular carcinoma and to elucidate its mechanism of action in cell culture. METHODS： The young transgenic mice were orally fed with the aqueous suspension of DL （400 mg/kg for 5 d/wk） for 15 wk and their liver was examined for histopathological changes at 20 wk. Serum levels of vascu- lar endothelial growth factor （VEGF） were also measured in these animals. To characterize the active fraction, DL was extracted with petroleum ether followed by methanol. The methanolic extract was sub-fractionated on a silica gel G column using a combination of non-polar and polar solvents and eleven fractions were obtained. Each fraction was analysed for cytotoxic effect on hepatoma （Huh7） and non-hepatoma （COS-1） cell lines and nontransformed hepatocytes （AML12） using tetrazolium （MTT） assay. Finally, the mechanism of cell death was investigated by measuring the levels of Bcl2, caspase 3 and DNA fragmentation. RESULTS： DL treatment of mice showed a complete protection against hepatocarcinogenesis. No adverse effect was observed in these animals. The serum VEGF level was significantly lowered in the treated mice as compared to control animals. Cell culture studies revealed that the methanolic extract of DL as well as its fraction 8 induced extensive cell death in both Huh-7 and COS-1 cells while AML12 cells were spared. This was accompanied by extensive fragmentation of DNA in Huh-7 and COS-1 cells. No change in the levels of canonical markers of apoptosis such as Bcl2 and caspase 3 was observed. CONCLUSION： DL of C. procera has the potential for anti-cancer therapy due to its differentJable targets and non-interference with regular pathway of apoptosis.
文摘Plant natural products including alkaloids,polyphenols,terpenoids and flavonoids have been reported to exert anticancer activity by targeting various metabolic pathways.The biological pathways regulated by plant products can serve as novel drug targets.Plant natural compounds or their derivatives used for cancer treatment and some novel plant-based compounds which are used in clinical trials were discussed.Callus suspension culture with secondary metabolites can provide a continuous source of plant pharmaceuticals without time and space limitations.Previous research has shown that rice callus suspension culture can kill>95%cancer cells with no significant effect on the growth of normal cells.The role of candidate genes and metabolites which are likely to be involved in the process and their potential to serve as anticancer and anti-inflammatory agents were discussed.Large scale production of plant callus suspension culture and its constituents can be achieved using elicitors which enhance specific secondary metabolites combined with bioprocess technology.
基金supported by National Science Foundation of China(Grant No.21671118)the Taishan Scholars Program.
文摘Herein,a new class of iridium(Ⅲ)-based metal complexes with phosphine-imine(P^N)ligands are synthesized and authenticated.These complexes show high cytotoxicities against seven cancer cells in vitro.Simultaneously,antitumor mechanism studies show that complex Ir3 induces apoptosis by depolarization of mitochondrial membrane potential,ROS overproduction and ROS-mediated DNA damage.Importantly,BIX01294,a G9a histone methyltransferase inhibitor,could markedly sensitize Ir3-induced cytotoxicity,cell cycle arrest,apoptosis and inhibition of migration in HCT116 cancer cells in vitro.Finally,we show that combined treatment with Ir3 and BIX01294 potently inhibits tumour growth and lung metastasis in vivo.Taken together,we demonstrate that BIX01294 could potently sensitize iridium(Ⅲ)-based metal complex-induced inhibition of tumour progression and provide the basis for developing new metal-based anticancer agents and therapeutic strategies in vivo for effective cancer therapy.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
基金National Natural Science Foundation of China (Grant No.20672008)985 Program of Ministry of Education of China.
文摘Aziridine and its N-substituted derivatives could undergo nucleophilic ring opening reaction with biological molecules, leading to their alkylation and the loss of their biological activities. For this purpose, ethyl 4-[N-methyl-N-（2,3-aziridinyl）amino] benzoate and diethyl N-{4-[N-methyl-N-（2,3-aziridinyl）amino]benzoyl}-L-glutamate, as the key intermediates in the synthesis of new anticancer agents, were designed and synthesized via four steps of reactions in good yields.
文摘Breast cancer is the most common cancer among women globally,where advancements in screening and treatment have significantly raised survival rates.The present investigation aims to identify the bioactive metabolites from Thalassia hemprichii and elucidate their mechanism through an integrated in vitro and in silico molecular docking approach.The crude extract has 27.2 mg GAE/g and 23.9 QE/g of phenolic and flavonoid content as revealed by preliminary phytochemical screening,which signifies and contributes better antioxidant properties.The anticancer assays demonstrated a significant reduction in the viability of breast cancer cell lines(MCF-7),with IC_(50) values(35.86μg/ml)indicating anticancer property.Mass spectroscopy data indicate the presence of 11 compounds,and these identified compounds demonstrate promising absorption and bioavailability scores based on Lipinski’s rules.Molecular docking studies suggested the high binding affinity of Betulin with key cancer-related proteins(e.g.,-9.28 kcal/mol with STAT3),highlighting its potential as a lead compound in breast cancer drug development.The pharmacological network is moderately significant and interacts with target proteins STAT3,SRC,EGFR,ESR1,HSP90AA1,HSP90AB2,PTGS2,GSK3B,MMP9,and CCND1.This research emphasizes the network pharmacology with in silico docking and in vitro assay validation to facilitate a comprehensive perspective of T.hemprichii extract against breast cancer with compound-target-pathway interrelations,indicating T.hemprichii as a possible multitargeting drug for breast cancer.Although these results show promise for seagrass as a potential therapeutic nutraceutical,further in vivo studies are important to understand the underlying molecular mechanisms in human metabolism.
基金support from the EPSRC(EP/G006792,EP/F034210/1 for PJS)University of Warwick(Chancellor’s International PhD Scholarship for HS)Anglo-American Platinum(HS)and Wellcome Trust(grant no 209173/Z/17/Z,Sir Henry Wellcome Fellowship for CI).
文摘Mono-axial functionalised octahedral diazido Pt(IV)complexes trans,trans,trans-[Pt(py)_(2)(N_(3))_(2)(OR_(1))(OR_(2))](OR_(1)=OH and OR_(2)=anticancer agent coumarin-3 carboxylate(cou,2a),pyruvate dehydrogenase kinase(PDK)inhibitors 4-phenylbutyrate(PhB,2b)or dichloroacetate(DCA,2c)),and their di-axial functionalised analogues with OR_(1)=DCA and OR_(2)=cou(3a),PhB(3b),or DCA(3c)have been synthesised and characterised,including the X-ray crystal structures of complexes 2a,3a,3b and 3c.These complexes exhibit dark stability and have the potential to generate cytotoxic Pt(II)species and free radicals selectively in cancer cells when irradiated.Mono-functionalised complexes 2a-2c showed higher aqueous solubility and more negative reduction potentials.Mono-and di-functionalised complexes displayed higher photocytotoxicity with blue light(1 h,465 nm,4.8 mW cm^(-2))than the parent dihydroxido complex 1(OR_(1)=OR_(2)=OH)in A2780 human ovarian(IC_(50)0.9-2.9μM for 2a-2c;0.11-0.39μM for 3a-3c)and A549 human lung cancer cells(5.4-7.8μM for 2a-2c;1.2-2.6μM for 3a-3c)with satisfactory dark stability.Notably,no apparent dark cytotoxicity was observed in healthy lung MRC-5 fibroblasts for all complexes(IC_(50)>20μM).Significantly higher platinum cellular accumulation and photo-generated ROS levels were observed for the di-functionalised complexes compared with their mono-functionalised analogues when cancer cells were treated under the same concentrations.
基金supported by the National Natural Science Foundation of China(Grant No.21401162)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.14KJB430024)+1 种基金Jiangsu Provincial Postdoctoral Sustentation Fund(Grant No.1402015B)support from the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Natural Science Foundation of Education Committee of Jiangsu Province(No.12KJB150023)is gratefully acknowledged.
文摘Transition metal complexes with substituted high affinity mixed ligands as potential anticancer agents can overcome the drawbacks of platinum-based drugs that are currently being marketed.Here,a new watersoluble asymmetric binuclear iminodiacetato-zinc(II)complex[Zn_(2)(ida)(phen)_(3)(NO_(3))]·NO_(3)·5H_(2)O(1)with a phenanthroline ligand has been synthesized and fully characterized with a wide range of analytical techniques including single crystal X-ray diffraction as well as spectroscopic techniques,such as FT-IR,UV/Vis,photoluminescence spectroscopy,and furthermore by elemental and thermogravimetric analyses.Moreover,unprecedented(H_(2)O)_(10)water clusters consisting of a quasi-planar tetramer and six dangling water molecules were observed in the void space of 3D supramolecular assemblies.The conversion behavior of(1)into two monomeric species[Zn(ida)(phen)(H_(2)O)](2)and[Zn(phen)_(2)(H_(2)O)_(2)]^(2+)(3)in aqueous solution was first studied by solid-state/solution NMR,ESI-MS,and solution UV/vis spectra.Next,these zinc(II)complexes(1-3),a mixture of(2)and(3)(mole ratio 1/1),ligands(phen and ida)and zinc ions(ZnCl_(2)and ZnSO_(4))were further evaluated for the in vitro cytotoxic profile in human hepatoma cell lines(HepG2 and SMMC-7721).We found that complex(1)effectively inhibited the proliferation of hepatocellular carcinoma cells,which is similar to a mixture of(2)and(3)in a 1:1 molar ratio,and IC50 values of(1)were almost about 20-50%of(2)or(3).Therefore,this binuclear complex(1)mainly acts as a cooperative inhibitor with complexes(2)and(3)toward tumor growth in solution.We further extended the preliminary research of complex(1)and found that(1)could induce cell cycle arrest at the G0/G1 phase.Additionally,overdosing on(1)exhibited low toxicity of mice(LD_(50)of(1)in ICR mice=736 mg kg^(-1),with 95%confidence interval 635-842 mg kg^(-1)).In conclusion,complex(1)with a high antitumor activity and low toxicity provides a new strategy for the treatment of liver cancer.
