A series of novel nitrogen-containing heterocyclic compounds based on the nitidine chloride(NC)core were designed and synthesized through the Heck reaction.The derivatives included sulfonamide analogs,piperazine analo...A series of novel nitrogen-containing heterocyclic compounds based on the nitidine chloride(NC)core were designed and synthesized through the Heck reaction.The derivatives included sulfonamide analogs,piperazine analogs,and thiazole analogs.Their antiproliferative activities were evaluated against four tumor cell lines(HL-60,HeLa,HepG2,H460)and normal liver cells(LO2)via in vitro cytotoxicity assays.The results showed that sulfonamide derivatives selectively inhibited HeLa cells.Among them,2,4,6-trimethyl-N-(6-(6-oxobenzo[c]phenanthridin-5(6H)-yl)hexyl)benzenesulfonamide(14c)exhibited the most potent activity[IC50=(1.83±0.24)μmol/L],comparable to nitidine chloride and cisplatin,while showing no significant toxicity toward LO2 cells.Piperazine analogs displayed broad inhibitory effects against tumor cells but accompanied by cytotoxicity,whereas thiazole analogs were largely inactive.Mechanistic studies revealed that the representative compound 14c exerted antitumor effects by inducing apoptosis and cell cycle arrest in HeLa cells,manifested by a significant reduction in the proportion of G0/G1 phase cells(69.90%±5.80%)and promotion of S/G2/M phase progression.The topoisomerase I(Topo I)inhibition assay demonstrated that the piperazine derivative effectively inhibits Topo I activity.Overall,compound 14c emerges as a promising antitumor candidate with high efficacy and low toxicity,demonstrating that nitrogen-containing hybridization of nitidine chloride provides a potential strategy for developing novel Topo I inhibitors.展开更多
The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predomi...The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.展开更多
Objectives:Prostate cancer cells often develop mechanisms to evade conventional therapies.Nanomedicine offers the potential for targeted drug delivery,improved tumor accumulation,and reduced systemic toxicity.This stu...Objectives:Prostate cancer cells often develop mechanisms to evade conventional therapies.Nanomedicine offers the potential for targeted drug delivery,improved tumor accumulation,and reduced systemic toxicity.This study biosynthesizes silver nanoparticles(NPP/AgONPs)functionalized with propolis,evaluates their antibacterial efficacy against uropathogenic strains of Escherichia coli(E.coli),and assesses their cytotoxic effect on cancer cell proliferation using the PC-3,human prostate epithelial cell line.Methods:The synthesized NPP/AgONPs physiochemical parameters were characterized,followed by in vitro assays to evaluate their antibacterial activity against multiple uropathogenic E.coli strains;determining the cytotoxicity against HPrEC and PC-3 cells by measuring cytotoxicity(CC_(50))and inhibition concentration(IC_(50)),respectively;analyzing cell cycle distribution and apoptosis via flow cytometry;and quantifying the reactive oxygen species(ROS),Caspase 3,and Caspase 8 expression in treated cells to elucidate mechanisms of cell death and growth inhibition.Results:NPP/AgONPs exhibited an average particle size of 22 nm,with four major X-ray diffraction(XRD)peaks corresponding to Joint Committee on Powder Diffraction Standards(JCPDS)No.01-1164,confirming their crystallinity.Moreover,the UV-vis absorbance at 390 nm yielded an energy gap of 2.45 eV.Antibacterial testing showed potent activity against the tested E.coli strains.In HPrEC and PC-3 cells,the CC_(50) was 262.04µg/mL,while the IC_(50) was 25.34μg/mL,respectively.Flow cytometry revealed increased apoptosis in the NPP/AgONPs-treated group across all stages,including early,late,and dead cells,compared with the controls.ROS,Caspase 3,and Caspase 8 levels were inflected in NPP/AgONPs-treated cells,showing apoptotic and growth-inhibitory effects.Conclusion:The propolis coating improves the nanoparticles’biocompatibility while enabling potent ROS-mediated apoptosis and cell-cycle disruption in PC-3 cells.These findings support the potential of NPP/AgONPs as a synergistic therapeutic platform,though optimization of dosing,detailed mechanism elucidation,and assessment of long-term safety are warranted.展开更多
Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive com...Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.展开更多
Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer ...Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.展开更多
Background:Since the launch of drug regulatory reform in 2015,China has substantially increased the availability of new cancer therapies.However,the efficacy evidence criteria for modified new anticancer drugs have no...Background:Since the launch of drug regulatory reform in 2015,China has substantially increased the availability of new cancer therapies.However,the efficacy evidence criteria for modified new anticancer drugs have not been evaluated.This cross-sectional study aimed to assess the pivotal trials supporting the indication approvals of innovative and modified new chemical anticancer drugs in China.Methods:The characteristics of indications,regulatory aspects,and pivotal trial designs were extracted and described.The primary efficacy endpoints of the pivotal clinical trials,including overall survival(OS)and progression-free survival(PFS),were quantitatively assessed by meta-analysis.Results:Between 2016 and 2022,77 cancer therapeutics for 107 indications were approved in China based on 128 pivotal trials.Among the 107 indications,64(59.8%)were classified as innovative anticancer drugs,and 43(40.2%)as modified new anticancer drugs.The study found that pivotal trials for innovative approvals tended to be single-arm trials,while modified approvals were more likely to employ randomized clinical trials with larger sample sizes and rigorous designs.Despite innovative drugs often receiving more expedited regulatory designations,there were no statistically significant differences in clinical benefit of OS or PFS outcomes between innovative and modified approvals.Conclusions:These results suggest that the current regulatory framework may prioritize the speed of approval for innovative drugs over the strength of supporting evidence.These findings align with the strategic trends of pharmaceutical companies and regulatory inclinations that aim to expedite the approval of innovative anticancer drugs with a high unmet need,thereby accelerating patients’accessibility to treatment.展开更多
Thank you for your thorough review and insightful comments on our research[1].Your observations are highly pertinent and provide valuable insights for our continued examination of China’s evolving anticancer drug reg...Thank you for your thorough review and insightful comments on our research[1].Your observations are highly pertinent and provide valuable insights for our continued examination of China’s evolving anticancer drug regulatory framework.展开更多
To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bisp...To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.展开更多
Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a...Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.展开更多
Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourc...Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.展开更多
Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the devel...Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.展开更多
Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the si...Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.展开更多
I read with great interest about a study that assessed the characteristics of pivotal trials with innovative and modified new anticancer drugs approved in China[1].In this letter,I reflect on the study designs of thes...I read with great interest about a study that assessed the characteristics of pivotal trials with innovative and modified new anticancer drugs approved in China[1].In this letter,I reflect on the study designs of these trials,given the context of oncology trial development in China and internationally.展开更多
Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of protein...Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of proteins in lung(A549)and colon(HT29)cancer cell lines was examined by using proteomics analysis.The protein-protein interaction study of differentially expressed proteins was done by using the Search Tool for the Retrieval of Interacting Genes(STRING),and the results showed that the proteins interacting with each other belong to different pathways.展开更多
Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB...Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB assay on six different human cancer cell lines. The results indicated that in the concentration of 10 μmol·L -1 the lead compound CAPE possessed anticancer activities against human HL 60, Bel 7402, and Hela cell lines, and two other compounds possessed potent anticancer activities against Bel 7402 and Hela cell lines.展开更多
Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cyt...Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.展开更多
A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer...A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer and human hepatic cancer cell lines, and compound 6, which is slightly different from 5 in its structure, showed good anticancer activity over human colorectal cancer cell line.展开更多
The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature....The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.展开更多
We investigated the redox status of H22 hepatocellular carcinoma xenografts treated with various doses of ethaselen, a novel anticancer drug targeting thioredoxin reductase （TrxR）. The concentrations of low molecula...We investigated the redox status of H22 hepatocellular carcinoma xenografts treated with various doses of ethaselen, a novel anticancer drug targeting thioredoxin reductase （TrxR）. The concentrations of low molecular weight antioxidant g!utathione （GSH） and malondialdehyde （MDA）, a product of lipid peroxidation, as well as the activities of important antioxidant enzymes were measured for elucidating the redox status of H22 tumor tissues. We found that the decreased GSH level, decreased thioredoxin reductase and superoxide dismutase （SOD） activities as well as increased MDA content were closely related to the tumor growth inhibition and ethaselen doses. Glutathione peroxidase （GPx） and glutathinne reductase （GR） activities are also affected by ethaselen treatment. However, the catalase （CAT） activity remains unchanged. Finally, we studied the relationship of tumor growth inhibition caused by ethaselen with these redox factors. This study showed that ethaselen could elevate the oxidative stress to suppress the H22 tumor growth in mice model.展开更多
文摘A series of novel nitrogen-containing heterocyclic compounds based on the nitidine chloride(NC)core were designed and synthesized through the Heck reaction.The derivatives included sulfonamide analogs,piperazine analogs,and thiazole analogs.Their antiproliferative activities were evaluated against four tumor cell lines(HL-60,HeLa,HepG2,H460)and normal liver cells(LO2)via in vitro cytotoxicity assays.The results showed that sulfonamide derivatives selectively inhibited HeLa cells.Among them,2,4,6-trimethyl-N-(6-(6-oxobenzo[c]phenanthridin-5(6H)-yl)hexyl)benzenesulfonamide(14c)exhibited the most potent activity[IC50=(1.83±0.24)μmol/L],comparable to nitidine chloride and cisplatin,while showing no significant toxicity toward LO2 cells.Piperazine analogs displayed broad inhibitory effects against tumor cells but accompanied by cytotoxicity,whereas thiazole analogs were largely inactive.Mechanistic studies revealed that the representative compound 14c exerted antitumor effects by inducing apoptosis and cell cycle arrest in HeLa cells,manifested by a significant reduction in the proportion of G0/G1 phase cells(69.90%±5.80%)and promotion of S/G2/M phase progression.The topoisomerase I(Topo I)inhibition assay demonstrated that the piperazine derivative effectively inhibits Topo I activity.Overall,compound 14c emerges as a promising antitumor candidate with high efficacy and low toxicity,demonstrating that nitrogen-containing hybridization of nitidine chloride provides a potential strategy for developing novel Topo I inhibitors.
基金supported by the National Key R&D Program of China(2024YFF1306700)the Key Project of Basic Research of Yunnan Province,China(202301AS070001)the Regional Innovative Development Joint Fund of NSFC(U23A20149).
文摘The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.
基金funded by Taibah University,Madinah,Kingdom of Saudi Arabia-with the grant number(447-16-1081).
文摘Objectives:Prostate cancer cells often develop mechanisms to evade conventional therapies.Nanomedicine offers the potential for targeted drug delivery,improved tumor accumulation,and reduced systemic toxicity.This study biosynthesizes silver nanoparticles(NPP/AgONPs)functionalized with propolis,evaluates their antibacterial efficacy against uropathogenic strains of Escherichia coli(E.coli),and assesses their cytotoxic effect on cancer cell proliferation using the PC-3,human prostate epithelial cell line.Methods:The synthesized NPP/AgONPs physiochemical parameters were characterized,followed by in vitro assays to evaluate their antibacterial activity against multiple uropathogenic E.coli strains;determining the cytotoxicity against HPrEC and PC-3 cells by measuring cytotoxicity(CC_(50))and inhibition concentration(IC_(50)),respectively;analyzing cell cycle distribution and apoptosis via flow cytometry;and quantifying the reactive oxygen species(ROS),Caspase 3,and Caspase 8 expression in treated cells to elucidate mechanisms of cell death and growth inhibition.Results:NPP/AgONPs exhibited an average particle size of 22 nm,with four major X-ray diffraction(XRD)peaks corresponding to Joint Committee on Powder Diffraction Standards(JCPDS)No.01-1164,confirming their crystallinity.Moreover,the UV-vis absorbance at 390 nm yielded an energy gap of 2.45 eV.Antibacterial testing showed potent activity against the tested E.coli strains.In HPrEC and PC-3 cells,the CC_(50) was 262.04µg/mL,while the IC_(50) was 25.34μg/mL,respectively.Flow cytometry revealed increased apoptosis in the NPP/AgONPs-treated group across all stages,including early,late,and dead cells,compared with the controls.ROS,Caspase 3,and Caspase 8 levels were inflected in NPP/AgONPs-treated cells,showing apoptotic and growth-inhibitory effects.Conclusion:The propolis coating improves the nanoparticles’biocompatibility while enabling potent ROS-mediated apoptosis and cell-cycle disruption in PC-3 cells.These findings support the potential of NPP/AgONPs as a synergistic therapeutic platform,though optimization of dosing,detailed mechanism elucidation,and assessment of long-term safety are warranted.
文摘Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.
基金supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020,accessed on 01 July 2025)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020,accessed on 01 July 2025).Institutional.
文摘Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.
基金supported by the Beijing Natural Science Foundation(L234038)the National Natural Science Foundation of China(no.82274015).
文摘Background:Since the launch of drug regulatory reform in 2015,China has substantially increased the availability of new cancer therapies.However,the efficacy evidence criteria for modified new anticancer drugs have not been evaluated.This cross-sectional study aimed to assess the pivotal trials supporting the indication approvals of innovative and modified new chemical anticancer drugs in China.Methods:The characteristics of indications,regulatory aspects,and pivotal trial designs were extracted and described.The primary efficacy endpoints of the pivotal clinical trials,including overall survival(OS)and progression-free survival(PFS),were quantitatively assessed by meta-analysis.Results:Between 2016 and 2022,77 cancer therapeutics for 107 indications were approved in China based on 128 pivotal trials.Among the 107 indications,64(59.8%)were classified as innovative anticancer drugs,and 43(40.2%)as modified new anticancer drugs.The study found that pivotal trials for innovative approvals tended to be single-arm trials,while modified approvals were more likely to employ randomized clinical trials with larger sample sizes and rigorous designs.Despite innovative drugs often receiving more expedited regulatory designations,there were no statistically significant differences in clinical benefit of OS or PFS outcomes between innovative and modified approvals.Conclusions:These results suggest that the current regulatory framework may prioritize the speed of approval for innovative drugs over the strength of supporting evidence.These findings align with the strategic trends of pharmaceutical companies and regulatory inclinations that aim to expedite the approval of innovative anticancer drugs with a high unmet need,thereby accelerating patients’accessibility to treatment.
文摘Thank you for your thorough review and insightful comments on our research[1].Your observations are highly pertinent and provide valuable insights for our continued examination of China’s evolving anticancer drug regulatory framework.
文摘To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.
基金Supported by Malaysian Ministry of Higher Education through the Fundamental Research Grant Scheme,No.FP103-2019.
文摘Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.
文摘Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.
文摘Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.
文摘Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.
文摘I read with great interest about a study that assessed the characteristics of pivotal trials with innovative and modified new anticancer drugs approved in China[1].In this letter,I reflect on the study designs of these trials,given the context of oncology trial development in China and internationally.
文摘Rice callus suspension culture(RCSC)has been shown to have anticancer activity based on cytotoxic activity on human colon and lung cancer cell lines.In the present study,the effect of RCSC on the expression of proteins in lung(A549)and colon(HT29)cancer cell lines was examined by using proteomics analysis.The protein-protein interaction study of differentially expressed proteins was done by using the Search Tool for the Retrieval of Interacting Genes(STRING),and the results showed that the proteins interacting with each other belong to different pathways.
文摘Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB assay on six different human cancer cell lines. The results indicated that in the concentration of 10 μmol·L -1 the lead compound CAPE possessed anticancer activities against human HL 60, Bel 7402, and Hela cell lines, and two other compounds possessed potent anticancer activities against Bel 7402 and Hela cell lines.
文摘Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.
基金New Teacher Foundation from Ministry of Education in China (Grant No.20090071120)Foundation of State Key Laboratory of Natural and Biomimetic Drugs (Grant No.K20100106)STCSM (Grant No.10431903200)
文摘A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer and human hepatic cancer cell lines, and compound 6, which is slightly different from 5 in its structure, showed good anticancer activity over human colorectal cancer cell line.
基金supported by the National Natural Science Foundation of China(82274085)the Natural Science Foundation of Jiangsu Province(BK20220478)the Natural Science Foundation of Jiangsu Higher Education institutions of China(22KJB360010).
文摘The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.
基金National Natural Science Foundation of China (Grant No.30472036).
文摘We investigated the redox status of H22 hepatocellular carcinoma xenografts treated with various doses of ethaselen, a novel anticancer drug targeting thioredoxin reductase （TrxR）. The concentrations of low molecular weight antioxidant g!utathione （GSH） and malondialdehyde （MDA）, a product of lipid peroxidation, as well as the activities of important antioxidant enzymes were measured for elucidating the redox status of H22 tumor tissues. We found that the decreased GSH level, decreased thioredoxin reductase and superoxide dismutase （SOD） activities as well as increased MDA content were closely related to the tumor growth inhibition and ethaselen doses. Glutathione peroxidase （GPx） and glutathinne reductase （GR） activities are also affected by ethaselen treatment. However, the catalase （CAT） activity remains unchanged. Finally, we studied the relationship of tumor growth inhibition caused by ethaselen with these redox factors. This study showed that ethaselen could elevate the oxidative stress to suppress the H22 tumor growth in mice model.
