In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evalu...In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.展开更多
Taking the six common anthocyanidins in nature, i.e. cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin, as examples, this paper summarized the main achievements about the structure-activity relatio...Taking the six common anthocyanidins in nature, i.e. cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin, as examples, this paper summarized the main achievements about the structure-activity relationships of the coloration and stability of anthocyanidins. The coloration and stability of anthocyanidins are funda- mentally determined by the chemical and spatial structures of the anthocyanidins. The electron-deficient state, hydroxylation and methylation patterns, especially the ones on the B-ring, and coplanarity of the three rings of anthocyanidins are inde- pendently or synergetically, positively and/or negatively, influence the coloration and stability of the anthocyanidins. Thereinto, the in vivo colorations of anthocyanins are also related to the organ-selective and crystal- or anthocyanic vacuolar inclusion- related existence of the anthocyanidins. This review could provide a reference for the researches of the structure-optimizing and function-exploiting of anthocyanidins and also for the selection of the crops and cultivars containing specific anthocyani- din profiles.展开更多
Aerogels are special porous materials with low thermal conductivity,light weight,high energy absorption rate and large surface area,which have been applied in many fields.However,controlling the aerogel microstructure...Aerogels are special porous materials with low thermal conductivity,light weight,high energy absorption rate and large surface area,which have been applied in many fields.However,controlling the aerogel microstructure remains an academic challenge.Herein,by employing graphene oxide(GO)as the aerogel skeleton and utilizing poly(vinyl alcohol)(PVA)to regulate the ice crystal growth,we elucidate the relationships between the physicochemical properties of GO/PVA aerogel precursors and the nucleation and growth of ice crystals by using an ice-templating method.We demonstrate that due to the hydrogen bond formed between PVA and water molecules,resulting in the initial crystallization temperature being reduced from-12.60℃(GO/PVA-0.01)to-16.21℃(GO/PVA-0.1).Meanwhile,the strong hydrogen bond between PVA and GO limits the diffusion of water molecules,thereby inhibiting the growth of ice crystals,decreasing the pore size of the GO/PVA aerogel from 9.96 nm(GO/PVA-0.01)to 7.19 nm(GO/PVA-0.3),and thus the compressive strength of the aerogel increases from 0.045 MPa to 0.13MPa.Overall,the finding of this study can be extended to other aerogel precursors,and exhibit important scientific value and practical significance for the preparation of aerogel materials with highly controllable structures and performances.展开更多
The growth of Staphylococcus aureus under the action of six kinds of Schiff bases（A,B,C,D,E,F） was studied by means of microcalorimetry. Growth constant k and inhibition ratio I were calculated. Also,the antibacteri...The growth of Staphylococcus aureus under the action of six kinds of Schiff bases（A,B,C,D,E,F） was studied by means of microcalorimetry. Growth constant k and inhibition ratio I were calculated. Also,the antibacterial activity,the action characteristics and the structure-activity relationships of the compounds on S. aureus were analyzed. Results indicate that B,F show good antibacterial activity（IC50：293.6 mg · L-1 and 307.8 mg · L-1） ,D,E show moderate antibacterial activity（IC50：966.3 mg · L-1 and 1 126.7 mg · L-1） ,and A,C just show weak antibacterial activity（IC50 〉1 200 mg · L-1） . The I-c curves mainly present a straight line shape for B,D,E and F,but an inverse ＂S＂ shape for A and C. Structure-activity relationships analysis suggests that the species and position of the substituents determine the antibacterial activity of these Schiff bases,and the charge density distribution is one of the most important influencing factors.展开更多
11β-Hydroxysteroid dehydrogenase 1(11β-HSD1)represents a promising drug target for metabolic syndrome,includ-ing obesity and type 2 diabetes.Our initial screen of a collection of natural products from Danshen led to...11β-Hydroxysteroid dehydrogenase 1(11β-HSD1)represents a promising drug target for metabolic syndrome,includ-ing obesity and type 2 diabetes.Our initial screen of a collection of natural products from Danshen led to the identi-fication of tanshinones as the potent and selective 11β-HSD1 inhibitors.To improve the druggability and explore the structure-activity relationships(SARs),more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials.More than 10 derivatives exhibited potent in vitro 11β-HSD1 inhibitory activity and good selectivity over 11β-HSD2 across human and mouse species.Based on the biological results,SARs were further discussed,which was also partially rationalized by a molecular docking model of 1 bound to the 11β-HSD1.Remarkably,compounds 1,17 and 30 significantly inhibited 11β-HSD1 in 3T3-L1 adipocyte and in livers of ob/ob mice,which merits further investigations as anti-diabetic agents.This study not only provides a series of novel selective 11β-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes,but also expands the boundaries of the chemical and biological spaces of tanshinones.展开更多
Fatty acids and derivatives(FADs)are resources for natural antimicrobials.In order to screen for additional potent antimicrobial agents,the antimicrobial activities of FADs against Staphylococcus aureus were examined ...Fatty acids and derivatives(FADs)are resources for natural antimicrobials.In order to screen for additional potent antimicrobial agents,the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay.Monoglycerides of fatty acids were the most potent class of fatty acids,among which monotridecanoin possessed the most potent antimicrobial activity.The conventional quantitative structure-activity relationship(QSAR)and comparative molecular field analysis(CoMFA)were performed to establish two statistically reliable models(conventional QSAR:R2=0.942,Q 2 LOO=0.910;CoMFA:R 2=0.979,Q 2=0.588,respectively).Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structureactivity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents.展开更多
Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison o...Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SitelD showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains （TM） among TM3, TM5, TM6, and TMT. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.展开更多
The relationships between the structure of oxime compounds(R^(1)R^(2)C=NOH,R^(1)/R^(2)=alkyl groups) with different substituents and their corresponding flotation performances were studied. The analyses of density fun...The relationships between the structure of oxime compounds(R^(1)R^(2)C=NOH,R^(1)/R^(2)=alkyl groups) with different substituents and their corresponding flotation performances were studied. The analyses of density functional theory(DFT) calculations illustrated that the introduced phenyl group at the R^(1) position could enhance the acidity,while the heptyl group could effectively increase the hydrophobicity and benefit van der Waals interactions. Meanwhile,the introduced amino group at the R^(2) position could provide cationic sites to interact with negatively charged surfaces of minerals, while the introduced hydroxyl group could provide additional action sites to form stable chelates with metal ions. Based on the structure-activity relationships, structural optimization was carried out to obtain three efficient collectors, which possessed superior flotation separation performances, proving the effectiveness of the structural modification to oxime compounds in this work.展开更多
The effects of eleven flavonoids on lipid peroxidation, protein degradation, deformability and osmotic fragility of human erythrocytes exposed in vitro to 10 mM H2O2 for 60 min at 37 oC have been studied. The followin...The effects of eleven flavonoids on lipid peroxidation, protein degradation, deformability and osmotic fragility of human erythrocytes exposed in vitro to 10 mM H2O2 for 60 min at 37 oC have been studied. The following flavonoids;quercetin, rutin and morin significantly protected eryt-hrocytes against lipid peroxidation caused by H2O2. This inhibition of lipid peroxidation could be explained by the presence of at least two hydroxyl groups in ring B of the flavonoid structure, regardless of their positions. However, the flavonoids;quercetin, 3,5,7-trihy- droxy-4'-methoxy flavone-7-rutinoside and 3- hydroxy flavone significantly protected eryt-hrocytes against protein degradation. This inhibition could also be explained by the presence of a hydroxyl group at C-3 in ring C of the flavonoid structure. Quercetin and 3,5,7-trihydroxy-4'- methoxy flvone-7-rutinoside significantly protected erythrocytes against loss of deformability and increased osmotic fragility, indicating that the loss of erythrocyte deformability and the increase in osmotic fragility of erythrocytes exposed to H2O2 are related to protein degradation rather than to lipid peroxidation. The other flavonoids (chrysin, 2-carboxy ethyl dihydroxy flavone, apigenin, cirsimaritin, α-naphto flavone and flavanone) failed to protect erythrocytes against the observed oxidative damages. The results demonstrate the importance of the chemical groups substituted on the basic skeleton of the flavonoids in dictating the type of antioxidant activity, and also demonstrate the hemorheological potentials of flavonoids that have particular protein-antioxidant activities.展开更多
In this study, solutions of hydrazine and its derivatives were irradiated using a pulsed electron beam to determine the half-reaction time of radiolysis. 3 D structures of the hydrazine derivatives were optimized, and...In this study, solutions of hydrazine and its derivatives were irradiated using a pulsed electron beam to determine the half-reaction time of radiolysis. 3 D structures of the hydrazine derivatives were optimized, and their energies were calculated using density functional theory with the B3 LYP method and 6-311 +(3 d, 3 p) basis set.For the first time, the 3 D quantitative structure-activity relationship(QSAR) equation describing the relationship between the hydrazine derivative structures and rate of radiolysis has been established using SPSS software.Pearson correlation analysis revealed a close correlation between the total energies of the molecules and half-reaction times. In the QSAR equation, Y =-7583.464 +54.687 X_1+94333.586 X_2,Y,X_1,and X_2 are the half-reaction time, total energy of the molecule, and orbital transition energy, respectively. The significance levels of the regression coefficients were 0.006 and 0.031, i.e., both less than 0.05. Thus, this model fully explains the relationship between hydrazine derivatives and β radiolysis stability.The results show that the total energy of the molecule and orbital transition energy are the main factors that influence the β radiolysis stability of these hydrazine derivatives.展开更多
Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment o...Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.展开更多
The physicochemical properties,structural characteristics,antioxidant,radioprotective and lipid-lowering activities,as well as the underlying structure-activity relationships of polysaccharides extracted from Nostoc f...The physicochemical properties,structural characteristics,antioxidant,radioprotective and lipid-lowering activities,as well as the underlying structure-activity relationships of polysaccharides extracted from Nostoc flagelliforme grown under normal(WL-EPS-1),salt stress(NaCl-EPS-1)and mixotrophic culture conditions(Glu-EPS-1)were studied.The results demonstrated that WL-EPS-1,NaCl-EPS-1 and Glu-EPS-1 were heteropolysaccharides comprising different proportions of monosaccharides and uronic acid,with different average molecular weights of 0.99×10^(3),1.09×10^(3)and 1.18×10^(3)kDa,respectively.Their intrinsic viscosity were significantly different,at 24.72,29.98,and 41.06 dL/g,respectively.The functional groups of polysaccharides were not greatly affected,but the chemical composition,triple-helix structure,chain length and surface morphology were significantly influenced by culture conditions.In vitro bioactivity assays showed that the antioxidant activity generally increased in the order of WL-EPS-1<NaCl-EPS-1<Glu-EPS-1,while NaCl-EPS-1 had the best radioprotective effect,and Glu-EPS-1 had the best lipid-lowering effect.In addition,the structure-activity relationship of the polysaccharides was analyzed by partial least squares,which revealed that the most important factors affecting the antioxidant,radioprotective and lipid-lowering activities of polysaccharides were viscosity and molecular weight.This study provides a strategy for obtaining high-bioactivity polysaccharides by appropriate regulation of culture conditions,as well as opening new directions for the molecular modification of polysaccharides.展开更多
The structural complexity of lithium-bearing clay minerals and limitations of conventional characterization methods impede efficient lithium extraction from montmorillonite-type ores.This study employs density functio...The structural complexity of lithium-bearing clay minerals and limitations of conventional characterization methods impede efficient lithium extraction from montmorillonite-type ores.This study employs density functional theory to elucidate structure-activity relationships governing lithium occurrence in montmorillonite,with particular emphasis on octahedral locking mechanisms and interfacial reaction barriers.Systematic calculations reveal four potential lithium occurrence sites:Al-O octahedra,Si-O tetrahedral lattices,interlayer sites and Li substituted H site.Lithium demonstrates optimal stability within Mg-Al-O octahedral lattices,exhibiting the lowest interaction energy(−672.982 kJ/mol)and substantial Mulliken charge transfer(2.35 e),confirming this configuration as the primary hosting environment.Density of states analysis uncovers critical electronic structure features:the 1s orbital of lithium remains energetically isolated from the Fermi level,explaining its chemical inertness and resistance to direct leaching.Conversely,the reactive 2p orbital of oxygen near the Fermi level facilitate surface interactions with flotation reagents.These electronic signatures imply the feasibility of flotation recovery alongside hydrometallurgical approaches.The octahedral locking mechanism originates from Li-induced dynamic symmetry reconstruction.This process achieves energy minimization through bond-angle regularization,while the notable contraction of Al-O/Mg-O bonds enhances electrostatic coupling.These synergistic effects ultimately establish a structural-charge dual-locking mechanism.This study delivers atomic-level insights into lithium occurrence mechanisms,addressing critical gaps in clay-type lithium mineralogy and revealing structure-activity relationships that guide sustainable lithium recovery via interface regulation.展开更多
Main observation and conclusion Methicillin-resistant Staphylococcus aureus(MRSA)has become a major threat on public health because of the increase of clinically isolated strains that exhibit resistance to many antibi...Main observation and conclusion Methicillin-resistant Staphylococcus aureus(MRSA)has become a major threat on public health because of the increase of clinically isolated strains that exhibit resistance to many antibiotics.Therefore,development of new antibiotics for the treatment of MRSA in-fection is a sustained challenge.We have previously identified a ring-opened bengamide analogue L472-2 that displays moderate ac-tivity against the growth of S.aureus.In our previous work,we started from L472-2 and identified a class of analogues containing al-kynyl groups which have the potential to activate SaCIpP activity but moderate antibacterial activity.Herein,we focused on the anti-bacterial activity of L472-2,and a novel series of ring-opened bengamide analogues were synthesized and their activities were evalu-ated against MRSA.By conducting a compact analysis of the structure-activity relationships(SAR)of these analogues,we found that an adamantane ethanol ester bengamide 2j showed excellent antibacterial activity towards six S.aureus strains,including MRSA,while it does not activate CIpP.Therefore,these bengamide analogues represent a new class of candidates that suppress MRSA via-bility..展开更多
This study preliminarily investigates the structure-activity relationships of novel [5,6]-fused ring energetic materials derived from the 6-nitro-7-azido-pyrazol [3,4-d][1,2,3]triazine 2-oxide(ICM-103) skeleton, empha...This study preliminarily investigates the structure-activity relationships of novel [5,6]-fused ring energetic materials derived from the 6-nitro-7-azido-pyrazol [3,4-d][1,2,3]triazine 2-oxide(ICM-103) skeleton, emphasizing the role of functional group substitution in tailoring key properties such as detonation performance and mechanical sensitivity. Strategic incorporation of nitrogen-rich substituents(e.g., hydrazine, guanidine) into the 1,2,3-triazine 2-oxide framework yielded compounds with diverse performance characteristics. Notably, compound 2 demonstrates energy performance(D = 8916 m·s^(-1) and P = 36.80 GPa) comparable to RDX, yet with lower mechanical sensitivity(IS = 37 J). Theoretical calculations show that the properties of the substituents themselves and their coupling with the molecular skeleton jointly determine the key properties of the target molecules. This study provides a framework for the customized design of energetic materials by linking the chemical properties of substituents with the performance parameters of target molecules. These findings highlight the potential of local molecular structural modification driven by structure-activity relationship analysis in promoting the development of next-generation energetic materials and lay a solid foundation for future research in this field.展开更多
QSARs (Quantitative structure-activity relationships) can provide correlations between the toxicity of a chemical and the physicochemical descriptors of the chemical. They can stimulate the development of toxicity dat...QSARs (Quantitative structure-activity relationships) can provide correlations between the toxicity of a chemical and the physicochemical descriptors of the chemical. They can stimulate the development of toxicity data by allowing estimations of toxicity to an organism to be made based on easily measured or calculated characteristics. In this note, we studied structure-activity relationships of chlorobenzenes, nitrobenzenes, anilines, phenols,展开更多
The use of quantitative structure-activity relationships (QSARs) started with the research into drugs and pesticides. It can be applied to predicting biological activity of new organic compounds from their molecular s...The use of quantitative structure-activity relationships (QSARs) started with the research into drugs and pesticides. It can be applied to predicting biological activity of new organic compounds from their molecular structure,or from their physicochemical parameters, andto direct synthesis of new drug and pesticide.展开更多
Density functional theory （DFT） was used to calculate molecular descriptors （properties） for 12 fluoro-quinolone with anti-S.pneumoniae activity. Principal component analysis （PCA） and hierarchical cluster analy...Density functional theory （DFT） was used to calculate molecular descriptors （properties） for 12 fluoro-quinolone with anti-S.pneumoniae activity. Principal component analysis （PCA） and hierarchical cluster analysis （HCA） were employed to reduce dimensionality and investigate in which variables should be more effective for classifying fluoroquinolones according to their degree of an-S.pneumoniae activity. The PCA results showed that the variables ELUMO, Q3, Q5, QA, logP, MR, VOL and △EHL of these compounds were responsible for the anti-S.pneumoniae activity. The HCA results were similar to those obtained with PCA.The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with antiS.pneumoniae activity. By using the chemometric results, 6 synthetic compounds were analyzed through the PCA and HCA and two of them are proposed as active molecules with anti-S.pneumoniae, which is consistent with the results of clinic experiments.展开更多
Demethoxylation was kinetically and spectroscopically studied over three catalysts with different Ru^(0)/Ru^(δ+) ratios.In-situ spectroscopic tests demonstrated that the synergy between Ru^(0)and Ru^(δ+) was crucial...Demethoxylation was kinetically and spectroscopically studied over three catalysts with different Ru^(0)/Ru^(δ+) ratios.In-situ spectroscopic tests demonstrated that the synergy between Ru^(0)and Ru^(δ+) was crucial,and Ru^(0) was in charge of H_(2) activation and adsorption of aromatic ring while Ru^(δ+) adsorbed with O in methoxyl.A Langmuir-Hinshelwood kinetic model was proposed,and ratio of Ru^(0)/Ru^(δ+) was the key in deciding the rate-determining step(RDS):i)desorp-tion of toluene was RDS over catalyst with highRu^(0)ratio;ii)dissociation of H_(2) was RDS over Ru^(δ+) enriched catalyst;iii)demethoxylation was rate-determined by CO water-gas shift (WGS) when Ru^(0)/Ru^(δ+) approached~1.The best perfor-mance was obtained over Ru/NiAl_(2)O_(4)-200,which effectively enabled both C-O bond activation and rapid recovery of adsorption sites for aromatic rings.Finally,in-situ DRIFT studies on methoxy decomposition and CO-WGS unraveled that the electronic composition of Ru was more stable in Ru/NiAl_(2)O_(4)-200 which contributes to its excellence.展开更多
In the past decade,the p53-MDM2 protein-protein interaction by small molecules has been confirmed as a successful strategy for cancer therapy.In our previous work,pyrrolo[3,4-c]pyrazol-6（1H）-ones were found to be po...In the past decade,the p53-MDM2 protein-protein interaction by small molecules has been confirmed as a successful strategy for cancer therapy.In our previous work,pyrrolo[3,4-c]pyrazol-6（1H）-ones were found to be potent p53-MDM2 inhibitors.Further optimization and structure-activity relationship studies were described in the present work.The result revealed that benzyl group on position N1 of imidazole and bromine on C4-phenyl of pyrrolidone showed higher inhibitory activities.In vitro antiproliferative assay demonstrated the potent p53-MDM2 inhibitor 5c with 4-fold selectivity for U2 OS and Saos-2 cells.These data indicated that 4,5-dihydropyrrolo[3,4-c]pyrazol-6（1H）-one moiety is a valuable scaffold for further development of p53-MDM2 inhibitors.展开更多
文摘In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.
基金Supported by the National Natural Science Foundation of China(31060045,31260091)~~
文摘Taking the six common anthocyanidins in nature, i.e. cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin, as examples, this paper summarized the main achievements about the structure-activity relationships of the coloration and stability of anthocyanidins. The coloration and stability of anthocyanidins are funda- mentally determined by the chemical and spatial structures of the anthocyanidins. The electron-deficient state, hydroxylation and methylation patterns, especially the ones on the B-ring, and coplanarity of the three rings of anthocyanidins are inde- pendently or synergetically, positively and/or negatively, influence the coloration and stability of the anthocyanidins. Thereinto, the in vivo colorations of anthocyanins are also related to the organ-selective and crystal- or anthocyanic vacuolar inclusion- related existence of the anthocyanidins. This review could provide a reference for the researches of the structure-optimizing and function-exploiting of anthocyanidins and also for the selection of the crops and cultivars containing specific anthocyani- din profiles.
基金financially supported by the National Natural Science Foundation of China(No.51873133)。
文摘Aerogels are special porous materials with low thermal conductivity,light weight,high energy absorption rate and large surface area,which have been applied in many fields.However,controlling the aerogel microstructure remains an academic challenge.Herein,by employing graphene oxide(GO)as the aerogel skeleton and utilizing poly(vinyl alcohol)(PVA)to regulate the ice crystal growth,we elucidate the relationships between the physicochemical properties of GO/PVA aerogel precursors and the nucleation and growth of ice crystals by using an ice-templating method.We demonstrate that due to the hydrogen bond formed between PVA and water molecules,resulting in the initial crystallization temperature being reduced from-12.60℃(GO/PVA-0.01)to-16.21℃(GO/PVA-0.1).Meanwhile,the strong hydrogen bond between PVA and GO limits the diffusion of water molecules,thereby inhibiting the growth of ice crystals,decreasing the pore size of the GO/PVA aerogel from 9.96 nm(GO/PVA-0.01)to 7.19 nm(GO/PVA-0.3),and thus the compressive strength of the aerogel increases from 0.045 MPa to 0.13MPa.Overall,the finding of this study can be extended to other aerogel precursors,and exhibit important scientific value and practical significance for the preparation of aerogel materials with highly controllable structures and performances.
基金Supported by the National Natural Science Foundation of China (20873096, 20621502)the Science and Technology Research Item of Hubei Provincial Department of Education (D20093103)
文摘The growth of Staphylococcus aureus under the action of six kinds of Schiff bases（A,B,C,D,E,F） was studied by means of microcalorimetry. Growth constant k and inhibition ratio I were calculated. Also,the antibacterial activity,the action characteristics and the structure-activity relationships of the compounds on S. aureus were analyzed. Results indicate that B,F show good antibacterial activity（IC50：293.6 mg · L-1 and 307.8 mg · L-1） ,D,E show moderate antibacterial activity（IC50：966.3 mg · L-1 and 1 126.7 mg · L-1） ,and A,C just show weak antibacterial activity（IC50 〉1 200 mg · L-1） . The I-c curves mainly present a straight line shape for B,D,E and F,but an inverse ＂S＂ shape for A and C. Structure-activity relationships analysis suggests that the species and position of the substituents determine the antibacterial activity of these Schiff bases,and the charge density distribution is one of the most important influencing factors.
基金the National Natural Science Foundation of China (No.U1502223)Hunan Provincial Key Research and Development Project (Grant No.2021WK2005 to X.Deng)+1 种基金Natural Science Foundation of Hunan Province (Grant No.2021JJ30894 to X.Deng)the open fund of State Key Laboratory of Phytochemistry and Plant Resource in West China (Grant No.P2020-KF03).
文摘11β-Hydroxysteroid dehydrogenase 1(11β-HSD1)represents a promising drug target for metabolic syndrome,includ-ing obesity and type 2 diabetes.Our initial screen of a collection of natural products from Danshen led to the identi-fication of tanshinones as the potent and selective 11β-HSD1 inhibitors.To improve the druggability and explore the structure-activity relationships(SARs),more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials.More than 10 derivatives exhibited potent in vitro 11β-HSD1 inhibitory activity and good selectivity over 11β-HSD2 across human and mouse species.Based on the biological results,SARs were further discussed,which was also partially rationalized by a molecular docking model of 1 bound to the 11β-HSD1.Remarkably,compounds 1,17 and 30 significantly inhibited 11β-HSD1 in 3T3-L1 adipocyte and in livers of ob/ob mice,which merits further investigations as anti-diabetic agents.This study not only provides a series of novel selective 11β-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes,but also expands the boundaries of the chemical and biological spaces of tanshinones.
基金Project(No.31071501)supported by the National Natural Science Foundation of China
文摘Fatty acids and derivatives(FADs)are resources for natural antimicrobials.In order to screen for additional potent antimicrobial agents,the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay.Monoglycerides of fatty acids were the most potent class of fatty acids,among which monotridecanoin possessed the most potent antimicrobial activity.The conventional quantitative structure-activity relationship(QSAR)and comparative molecular field analysis(CoMFA)were performed to establish two statistically reliable models(conventional QSAR:R2=0.942,Q 2 LOO=0.910;CoMFA:R 2=0.979,Q 2=0.588,respectively).Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structureactivity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents.
基金supported by the National Natural Science Foundation of China(Molecular design,catalysis and synthesis methods of novel fentanyl analogs active compounds)No.20872095
文摘Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SitelD showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains （TM） among TM3, TM5, TM6, and TMT. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.
基金the support of the National Natural Science Foundation of China(Nos.51774329 and 51904337)the High Performance Computing Center of Central South University,China。
文摘The relationships between the structure of oxime compounds(R^(1)R^(2)C=NOH,R^(1)/R^(2)=alkyl groups) with different substituents and their corresponding flotation performances were studied. The analyses of density functional theory(DFT) calculations illustrated that the introduced phenyl group at the R^(1) position could enhance the acidity,while the heptyl group could effectively increase the hydrophobicity and benefit van der Waals interactions. Meanwhile,the introduced amino group at the R^(2) position could provide cationic sites to interact with negatively charged surfaces of minerals, while the introduced hydroxyl group could provide additional action sites to form stable chelates with metal ions. Based on the structure-activity relationships, structural optimization was carried out to obtain three efficient collectors, which possessed superior flotation separation performances, proving the effectiveness of the structural modification to oxime compounds in this work.
文摘The effects of eleven flavonoids on lipid peroxidation, protein degradation, deformability and osmotic fragility of human erythrocytes exposed in vitro to 10 mM H2O2 for 60 min at 37 oC have been studied. The following flavonoids;quercetin, rutin and morin significantly protected eryt-hrocytes against lipid peroxidation caused by H2O2. This inhibition of lipid peroxidation could be explained by the presence of at least two hydroxyl groups in ring B of the flavonoid structure, regardless of their positions. However, the flavonoids;quercetin, 3,5,7-trihy- droxy-4'-methoxy flavone-7-rutinoside and 3- hydroxy flavone significantly protected eryt-hrocytes against protein degradation. This inhibition could also be explained by the presence of a hydroxyl group at C-3 in ring C of the flavonoid structure. Quercetin and 3,5,7-trihydroxy-4'- methoxy flvone-7-rutinoside significantly protected erythrocytes against loss of deformability and increased osmotic fragility, indicating that the loss of erythrocyte deformability and the increase in osmotic fragility of erythrocytes exposed to H2O2 are related to protein degradation rather than to lipid peroxidation. The other flavonoids (chrysin, 2-carboxy ethyl dihydroxy flavone, apigenin, cirsimaritin, α-naphto flavone and flavanone) failed to protect erythrocytes against the observed oxidative damages. The results demonstrate the importance of the chemical groups substituted on the basic skeleton of the flavonoids in dictating the type of antioxidant activity, and also demonstrate the hemorheological potentials of flavonoids that have particular protein-antioxidant activities.
文摘In this study, solutions of hydrazine and its derivatives were irradiated using a pulsed electron beam to determine the half-reaction time of radiolysis. 3 D structures of the hydrazine derivatives were optimized, and their energies were calculated using density functional theory with the B3 LYP method and 6-311 +(3 d, 3 p) basis set.For the first time, the 3 D quantitative structure-activity relationship(QSAR) equation describing the relationship between the hydrazine derivative structures and rate of radiolysis has been established using SPSS software.Pearson correlation analysis revealed a close correlation between the total energies of the molecules and half-reaction times. In the QSAR equation, Y =-7583.464 +54.687 X_1+94333.586 X_2,Y,X_1,and X_2 are the half-reaction time, total energy of the molecule, and orbital transition energy, respectively. The significance levels of the regression coefficients were 0.006 and 0.031, i.e., both less than 0.05. Thus, this model fully explains the relationship between hydrazine derivatives and β radiolysis stability.The results show that the total energy of the molecule and orbital transition energy are the main factors that influence the β radiolysis stability of these hydrazine derivatives.
基金the National Natural Science Foundation of China(No.32272575)National College Student Innovation and Entrepreneurship Training Program(No.202210459164)for financial support.
文摘Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.
基金support from the National Natural Science Foundation of China(32172191)the Tianjin Research Innovation Project for Postgraduate Students(2021YJSB211).
文摘The physicochemical properties,structural characteristics,antioxidant,radioprotective and lipid-lowering activities,as well as the underlying structure-activity relationships of polysaccharides extracted from Nostoc flagelliforme grown under normal(WL-EPS-1),salt stress(NaCl-EPS-1)and mixotrophic culture conditions(Glu-EPS-1)were studied.The results demonstrated that WL-EPS-1,NaCl-EPS-1 and Glu-EPS-1 were heteropolysaccharides comprising different proportions of monosaccharides and uronic acid,with different average molecular weights of 0.99×10^(3),1.09×10^(3)and 1.18×10^(3)kDa,respectively.Their intrinsic viscosity were significantly different,at 24.72,29.98,and 41.06 dL/g,respectively.The functional groups of polysaccharides were not greatly affected,but the chemical composition,triple-helix structure,chain length and surface morphology were significantly influenced by culture conditions.In vitro bioactivity assays showed that the antioxidant activity generally increased in the order of WL-EPS-1<NaCl-EPS-1<Glu-EPS-1,while NaCl-EPS-1 had the best radioprotective effect,and Glu-EPS-1 had the best lipid-lowering effect.In addition,the structure-activity relationship of the polysaccharides was analyzed by partial least squares,which revealed that the most important factors affecting the antioxidant,radioprotective and lipid-lowering activities of polysaccharides were viscosity and molecular weight.This study provides a strategy for obtaining high-bioactivity polysaccharides by appropriate regulation of culture conditions,as well as opening new directions for the molecular modification of polysaccharides.
基金support by Yunnan Provincial Science and Technology Department(grant No.202301AS070033)is sincerely appreciated。
文摘The structural complexity of lithium-bearing clay minerals and limitations of conventional characterization methods impede efficient lithium extraction from montmorillonite-type ores.This study employs density functional theory to elucidate structure-activity relationships governing lithium occurrence in montmorillonite,with particular emphasis on octahedral locking mechanisms and interfacial reaction barriers.Systematic calculations reveal four potential lithium occurrence sites:Al-O octahedra,Si-O tetrahedral lattices,interlayer sites and Li substituted H site.Lithium demonstrates optimal stability within Mg-Al-O octahedral lattices,exhibiting the lowest interaction energy(−672.982 kJ/mol)and substantial Mulliken charge transfer(2.35 e),confirming this configuration as the primary hosting environment.Density of states analysis uncovers critical electronic structure features:the 1s orbital of lithium remains energetically isolated from the Fermi level,explaining its chemical inertness and resistance to direct leaching.Conversely,the reactive 2p orbital of oxygen near the Fermi level facilitate surface interactions with flotation reagents.These electronic signatures imply the feasibility of flotation recovery alongside hydrometallurgical approaches.The octahedral locking mechanism originates from Li-induced dynamic symmetry reconstruction.This process achieves energy minimization through bond-angle regularization,while the notable contraction of Al-O/Mg-O bonds enhances electrostatic coupling.These synergistic effects ultimately establish a structural-charge dual-locking mechanism.This study delivers atomic-level insights into lithium occurrence mechanisms,addressing critical gaps in clay-type lithium mineralogy and revealing structure-activity relationships that guide sustainable lithium recovery via interface regulation.
基金the Science and Technology Commission of Shanghai Municipality(No.16ZR1407000)the National Natural Science Foundation of China(Nos.81861138046 and 21725801).
文摘Main observation and conclusion Methicillin-resistant Staphylococcus aureus(MRSA)has become a major threat on public health because of the increase of clinically isolated strains that exhibit resistance to many antibiotics.Therefore,development of new antibiotics for the treatment of MRSA in-fection is a sustained challenge.We have previously identified a ring-opened bengamide analogue L472-2 that displays moderate ac-tivity against the growth of S.aureus.In our previous work,we started from L472-2 and identified a class of analogues containing al-kynyl groups which have the potential to activate SaCIpP activity but moderate antibacterial activity.Herein,we focused on the anti-bacterial activity of L472-2,and a novel series of ring-opened bengamide analogues were synthesized and their activities were evalu-ated against MRSA.By conducting a compact analysis of the structure-activity relationships(SAR)of these analogues,we found that an adamantane ethanol ester bengamide 2j showed excellent antibacterial activity towards six S.aureus strains,including MRSA,while it does not activate CIpP.Therefore,these bengamide analogues represent a new class of candidates that suppress MRSA via-bility..
基金financial support from the National Natural Science Foundation of China (Grant No.22375190)。
文摘This study preliminarily investigates the structure-activity relationships of novel [5,6]-fused ring energetic materials derived from the 6-nitro-7-azido-pyrazol [3,4-d][1,2,3]triazine 2-oxide(ICM-103) skeleton, emphasizing the role of functional group substitution in tailoring key properties such as detonation performance and mechanical sensitivity. Strategic incorporation of nitrogen-rich substituents(e.g., hydrazine, guanidine) into the 1,2,3-triazine 2-oxide framework yielded compounds with diverse performance characteristics. Notably, compound 2 demonstrates energy performance(D = 8916 m·s^(-1) and P = 36.80 GPa) comparable to RDX, yet with lower mechanical sensitivity(IS = 37 J). Theoretical calculations show that the properties of the substituents themselves and their coupling with the molecular skeleton jointly determine the key properties of the target molecules. This study provides a framework for the customized design of energetic materials by linking the chemical properties of substituents with the performance parameters of target molecules. These findings highlight the potential of local molecular structural modification driven by structure-activity relationship analysis in promoting the development of next-generation energetic materials and lay a solid foundation for future research in this field.
基金Project supported by the National Natural Science Foundation of China.
文摘QSARs (Quantitative structure-activity relationships) can provide correlations between the toxicity of a chemical and the physicochemical descriptors of the chemical. They can stimulate the development of toxicity data by allowing estimations of toxicity to an organism to be made based on easily measured or calculated characteristics. In this note, we studied structure-activity relationships of chlorobenzenes, nitrobenzenes, anilines, phenols,
基金Project supported by the National Natural Science Foundation of China.
文摘The use of quantitative structure-activity relationships (QSARs) started with the research into drugs and pesticides. It can be applied to predicting biological activity of new organic compounds from their molecular structure,or from their physicochemical parameters, andto direct synthesis of new drug and pesticide.
基金This work was supported by National Nature Science Foundation of China and China Academy of Engineering Physics （No. 10376021） Provincial National Science Foundation of He＇nan （No. 2004601107）.
文摘Density functional theory （DFT） was used to calculate molecular descriptors （properties） for 12 fluoro-quinolone with anti-S.pneumoniae activity. Principal component analysis （PCA） and hierarchical cluster analysis （HCA） were employed to reduce dimensionality and investigate in which variables should be more effective for classifying fluoroquinolones according to their degree of an-S.pneumoniae activity. The PCA results showed that the variables ELUMO, Q3, Q5, QA, logP, MR, VOL and △EHL of these compounds were responsible for the anti-S.pneumoniae activity. The HCA results were similar to those obtained with PCA.The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with antiS.pneumoniae activity. By using the chemometric results, 6 synthetic compounds were analyzed through the PCA and HCA and two of them are proposed as active molecules with anti-S.pneumoniae, which is consistent with the results of clinic experiments.
基金supported financially by the National Key Research and Development Program of China(No.2022YFA1504900)the NSFC of China(No.22072041,21832002)the Science and Technology Commission of Shanghai Municipality(10dz2220500).
文摘Demethoxylation was kinetically and spectroscopically studied over three catalysts with different Ru^(0)/Ru^(δ+) ratios.In-situ spectroscopic tests demonstrated that the synergy between Ru^(0)and Ru^(δ+) was crucial,and Ru^(0) was in charge of H_(2) activation and adsorption of aromatic ring while Ru^(δ+) adsorbed with O in methoxyl.A Langmuir-Hinshelwood kinetic model was proposed,and ratio of Ru^(0)/Ru^(δ+) was the key in deciding the rate-determining step(RDS):i)desorp-tion of toluene was RDS over catalyst with highRu^(0)ratio;ii)dissociation of H_(2) was RDS over Ru^(δ+) enriched catalyst;iii)demethoxylation was rate-determined by CO water-gas shift (WGS) when Ru^(0)/Ru^(δ+) approached~1.The best perfor-mance was obtained over Ru/NiAl_(2)O_(4)-200,which effectively enabled both C-O bond activation and rapid recovery of adsorption sites for aromatic rings.Finally,in-situ DRIFT studies on methoxy decomposition and CO-WGS unraveled that the electronic composition of Ru was more stable in Ru/NiAl_(2)O_(4)-200 which contributes to its excellence.
基金supported in part by the National Natural Science Foundation of China (Nos. 81373331 and 81502978)the Bio-Pharmaceutical Project of Science and Technology of Shanghai (No. 14431902300)Youth grant of Second Military Medical University (No. 2014QN08)
文摘In the past decade,the p53-MDM2 protein-protein interaction by small molecules has been confirmed as a successful strategy for cancer therapy.In our previous work,pyrrolo[3,4-c]pyrazol-6（1H）-ones were found to be potent p53-MDM2 inhibitors.Further optimization and structure-activity relationship studies were described in the present work.The result revealed that benzyl group on position N1 of imidazole and bromine on C4-phenyl of pyrrolidone showed higher inhibitory activities.In vitro antiproliferative assay demonstrated the potent p53-MDM2 inhibitor 5c with 4-fold selectivity for U2 OS and Saos-2 cells.These data indicated that 4,5-dihydropyrrolo[3,4-c]pyrazol-6（1H）-one moiety is a valuable scaffold for further development of p53-MDM2 inhibitors.
