Advances in Research of Biological Activity,Action Mechanism and Structure-Activity Relationship of Lentinan

Lentinula edodes is the second largest edible mushroom in the world and is widely used as food and medicine.Modern research shows that lentinan(LNT)is the main active component of L.edodes.It has anti-cancer,treatment of diabetes,intestinal protection,anti-inflammatory,anti-oxidation,anti-aging,hepatoprotective,immune-regulating effects.In this review,the biological activity,action mechanism and structure-activity relationship of LNT in recent years are reviewed.On this basis,the existing problems were discussed,and the future research and application of LNT were prospected.Finally,it is hoped that this review will promote the in-depth study of LNT and provide a reference for its development as a drug and functional food.

Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus

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.

Quantum Chemical Study on Structure-activity Relationship of Several Kinds of Drugs

The structure-activity relationship of several drugs with similar structure has been investigated by using ab initio method. The relation between the dipole moments and biological activities of these drugs was judged after comparing their geometric structures, dipole moments and inhibitory concentrations. In principle, new drug molecule could be reasonably designed by altering the place of groups and ultimately, the potential drug could be screened by comparing the dipole moments of obtained molecules.

Support vector classification for structure-activity-relationship of 1-（ 1H- 1,2,4-triazole- 1-yl）- 2-（ 2,4-difluorophenyl）-3-substituted-2- propanols

The support vector classification （SVC） was employed to make a model for classification of antifungal activities of 1-（1H-1,2,4-triazole-l-yl）-2-（2,4-difluorophenyl）-3-substituted-2-propanols triazole derivatives. The compounds with high antifungal activities and those with low antifungal activities were compared on the basis of the following molecular descriptors： net atomic charge on the atom N connecting with R, dipole moment and heat of formation, By using the SVC, a mathematical model was constructed, which can predict the antifungal activities of the triazole derivatives, with an accuracy of 91% on the basis of the leave-one-out cross-validation （LOOCV） test, The results indicate that the performance of the SVC model can exceed that of the principal component analysis （PCA） and K-Nearest Neighbor （KNN） models for this real world data set.

Proposal and evaluation of a new norm index-based QSAR model to predict pEC50 and pCC50 activities of HEPT derivatives

The search and development of anti-HIV drugs is currently one of the most urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship （QSAR） model based on some new norm indexes, was obtained to a series of more than 150 HEPT derivatives （1-[（2-hydroxyethoxy）methyl]-6-（phenylthio）thymine） to find their pEC50 （the required effective concentration to achieve 50% protection of MT-4 cells against the cytopathic effect of virus） and pCC50 （the required cytotoxic concentration to reduce visibility of 50% mock infected cell） activities. The model efficiencies were then validated using the leave-one-out cross validation （LOO-CV） and y- randomization test. Results indicated that this new model was efficient and could provide satisfactory results for prediction of pECso and pCC50 with the higher R2 train and the higher Rt2est. By using the leverage approach, the applicability domain of this model was further investigated and no response outlier was detected for HEFT derivatives involved in this work. Comparison results with reference methods demonstrated that this new method could result in significant improvements for predicting pEC50 and pCC50 of anti-HIV HEPT derivatives. Moreover, results shown in this present study suggested that these two absolutely different activities pECso and pCC50 of anti-HIV HEPT derivatives could be predicted well with a totally similar QSAR model, which indicated that this model mizht have the potential to be further utilized for other biological activities of HEFT derivatives.

Panaxadiol and Panaxatriol Derivatives as Anti-Hepatitis B Virus Inhibitors

28 Derivatives of panaxadiol(PD)and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells,of which 17 derivatives inhibited HBV DNA replication.Compounds 4,9,10,14,and 15 showed moderate activity against HBV DNA replication with IC50 values ranged from 7.27 to 28.21 lM compared with PD.In particular,3-O-20-thenoyl panaxadiol(4)inhibited not only HBV DNA replication(IC50=16.5 lM,SI[115.7)but also HBsAg(IC50=30.8 lM,SI[62.0)and HBeAg(IC50=18.2 lM,SI[105.14)secretions.Their structure–activity relationships were discussed for guiding future research toward the discovery of new anti-HBV agents.

Synthesis of novel N-pyridylpyrazole derivatives containing 1,2,4-oxadiazole moiety via 1,3-dipolar cycloaddition and their structures and biological activities

A series of novel 1,2,4-oxadiazole-containing N-pyridylpyrazole derivatives 12 a-h were efficiently synthesized with pivaldehyde,pyridylpyrazole carboxylic acid and arylamine as raw materials via 1,3-dipolar cycloaddition.Their structures were identified by melting points,1 H NMR,13 C NMR and elemental analysis or HRMS.The exploration on the single-crystal structures of 12 c and 12 g revealed the stereochemical and substituent oriental characteristics,and the relevance of the structure and the reaction activity of this type of compounds.The preliminary bioassays indicated that several compounds had good insecticidal activities,among which 12 c showed a lethality rate of 80%towards Mythimna separata Walker at 200μg/mL;some of the compounds exhibited favorable fungicidal activities at 50μg/mL against Physalospora piricola,Rhizoctonia cereal,Sclerotinia sclerotiorum,etc.Among which,12 a,12 b,12 c and 12 h could be considered as new fungicidal leading compounds for further structural optimization.These discoveries along with the structure-activity relationship analysis in this paper will provide useful guidance for the innovative studies on new pyridylpyrazole derivatives and their applications in agrochemical area.

Synthesis and structure-insecticidal activity relationship of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety

A series of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety,i.e.,diamides 11,simple aryl-bearing amides 12 and acylthioureas 14 were successfully synthesized based on the key fluo ro-containing phe nylpyrazole acid intermediate.The new compounds were identified and confirmed by melting point,1H NMR,13C NMR and elemental analysis or HRMS.The bioassay results indicated that some of the compounds possessed excellent insecticidal activities towards oriental armyworm,diamondback moth and corn borer at low concentrations.For examples,compounds 11a,11e-g and 14b exhibited remarkable larvicidal activities with LC50 values of 0.13-0.39 mg/L and 0.0002-0.0014 mg/L against oriental armyworm and diamondback moth,respectively,were comparable with those of the control chlorantraniliprole.Particularly,lie were found superior to chlorantraniliprole in oriental armyworm tests(LC50:0.23 mg/L vs.0.26 mg/L);11a,lie,11f and 14c in diamondback moth tests with LC50 values of 0.0002 mg/L,0.0002 mg/L,0.0008 mg/L and 0.0005 mg/L,respectively,we re more effective than that of chlorantraniliprole.In addition,12 a also showed a promising insecticidal potential and development/optimization advantage.Compounds 11a,lle-g,12a,14b and 14c could be considered as possible new leading structures for further study.The SAR investigation indicated that the compounds with fluorine motif(e.g.,-F,-CF2H,-CF3)held apparently favorable insecticidal potentials,which provided useful guidance for further design/development of new phenylpyrazole-containing agrochemicals.

Hydrazone derivatives in agrochemical discovery and development

As a common active substructure,hydrazone has attracted increasing attention and is considered essential for pesticide discovery.It has been widely regarded as a potential insecticidal,antibacterial,antifungal,antiviral,and herbicidal agent.In this review,we highlight the pesticide versatility of hydrazone fragments and provide a comprehensive summary of the biological activity,structure-activity relationship analysis(SARs),and primary mechanism of their analogs.This profile is expected to give valuable information for discovering new pesticides.

Indole derivatives as agrochemicals:An overview

Indole is a biologically active compound formed by the fusion of benzene and pyrrole,and it is widely found in natural products and drugs.Due to the unique structure and properties of indole,its derivatives often exhibit distinctive physiological activities,which has led to widespread attention in the field of pesticide development.Analyzing the design strategies and structure-activity relationships(SARs)of compounds is a crucial step in developing novel pesticides.This review mainly summarizes indole compounds with plant growth regulating,antiviral,fungicidal,herbicidal,and insecticidal activities,with the aim of providing new insights into the discovery and mechanism of action of novel indole-based pesticides.

Recent advances on application of polysaccharides in cosmetics

Natural products have attracted wide attention in the cosmetics market due to their safety and high efficiency.As a highly active substance in nature,natural polysaccharides have been reported in recent years to have various cosmetic activities such as moisturizing,whitening,anti-aging and repairing skin,and are becoming a hot research topic in the cosmetics industry.At present,the mechanism of polysaccharide exerting cosmetic activity has been widely studied,but the relationship between polysaccharide’s chemical structure and cosmetic activity has not been effectively analyzed,which leads to the limitation of polysaccharide development.In this review,the mechanism of polysaccharides exerting cosmetic activities such as moisturizing,whitening,anti-aging and skin repair was introduced.The potential relationship between the structure and activity of polysaccharides was summarized by analyzing the influence of physical and chemical properties of polysaccharides,such as extraction method,molecular weight,monosaccharide composition,functional group and structural modification,etc.,which laid a foundation for the analysis of the structure-activity relationship of polysaccharides and improved its cosmetic value.

Synthesis, Nematicidal Activity, and 3D-QSAR of Novel 1,3,4-Oxadiazole/ Thiadiazole Thioether Derivatives

Forty one novel 1,3,4-oxadiazole/thiadiazole thioether derivatives containing phenoxy moiety were designed and synthesized. Bioassay demonstrated that some of them showed remarkable activities against Tylenchufus semipenetruns in vitro and in vivo. Compounds 20, 21, 35 and 39 showed excellent lethal activities after treatment for 48 h in vitro, with LC50 values of 13.4±1.8, 11.7±2.5, 13.7±2.4 and 13.31.1 mg.L-1, respectively, which were obviously superior to fosthiazate （49.1±2.8 mg.L-1） and avermectin （26.6±2.3 mg.L-1）. Compound 23. can effectively control the citrus nema- tode disease caused by T. semipenetruns at 200 mg.L-1 in vivo with （68±3）% inhibitory effect, which was even better than that of avermectin （（63±2）%）. The CoMFA and CoMSIA models of three-dimensional quantitative structure-activity relationships （3D-QSARs） were established. The compound 33 was designed based on the 3D-QSAR models with more vigorous nematicidal activities in vitro （LC50：9.8±1.4 mg.L-1） and in vivo （（70±5）%）. These results demonstrated that compound 33 can be considered as a potential nematicide.

Design, synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines

A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines（PC-3, LNCa P, and DU145） were evaluated by a CCK-8 assay. Compounds 8, 10, 13, 17 and 20 exhibited strong cytotoxic activities against the tested cancer cell lines（IC_（50）〈3 μmol/L）. In addition, these compounds exhibited weak cytotoxic effects on human epithelial prostate normal cells WPMY-1. The structure-activity relationship（SAR） of these arylpiperazine derivatives was also discussed based on the obtained experimental data.

Synthesis and cytotoxic activity of 3, 4, 11-trihydroxyl modified derivatives of bergenin

To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted(3a, 4a, 5a, 6a, 7a) and doublysubstituted(8b, 9b) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.

Design, Synthesis, and Evaluation of Fungicidal Activity of Novel Pyrazole-Containing Strobilurin Derivatives

In searching for novel fungicidal leads,a series of pyrazole-containing strobilurins were rationally designed,synthesized and charac-terized.Bioassay indicated that compound 1-7 displayed excellent fungicidal activity against a broad spectrum of plant pathogens such as Gibberella zeae,Rhizoctonia cereolis,Sclerotinia sclerotiorum,Phytophthora infestans,Physolosporo piricola and Pellicularia sosakii with EC_(50) of 0.16,0.02,0.72,0.07,0.77 and 0.65μg/mL,respectively,which were 3-10 times more potent than the positive control azoxystrobin against the corresponding pathogens.Moreover,like azoxystrobin and kresoxim methyl,1-7,displayed excellent protec-tive activity against P.sorghi.Molecular docking validated that 1-7 and azoxystrobin would share a similar binding mode with cytochrome bc_(1) complex.This study demonstrates that 1-7 is a promising fungicidal candidate for further development.

Synthesis and biological evaluation of indole-3-carboxamide derivatives as antioxidant agents

Oxidative stress results in various pathologies and as consequence antioxidant agents have attracted uninterrupted attention.In this paper,a novel series of indole-3-carboxamide derivatives(6 a-61) were designed and synthesized based on the melatonin structure as novel antioxidants.All of them were evaluated for the antioxidant activities in vitro against human neuroblastoma SH-SY5 Y cell line using H2 O2 radical scavenging assay.The target compounds 6 a,6 f and 6 i indicated better activities than the positive control,ascorbic acid,and 6 a exhibited the best antioxidant activity.In addition,the structureactivity relationships of the target compounds were also preliminarily summarized based on the obtained experimental data.

6-N杂环取代血根碱衍生物的合成、结构表征、生物活性与构效关系

以血根碱为先导,通过活性基团拼接方法,设计合成了一类结构新颖的6-N杂环取代血根碱衍生物.目标化合物的结构均通过核磁共振波谱(NMR)、红外光谱(IR)和高分辨质谱(HRMS)确证.采用生长速率法测定了目标化合物的体外抑菌活性,并对其构效关系进行了分析.初步抑菌活性测试结果表明,目标化合物3a-06,3a-07, 3b-01, 3c-07和3c-08对10种供试病原菌表现出相对广谱的抑菌活性,在50μg/mL浓度下,对多数供试病原菌抑制率在72%以上.精密毒力测定结果显示,部分目标化合物表现出优良的抑菌活性.化合物3b-01对茶叶炭疽病菌和棉花立枯病菌的半最大效应浓度(EC_(50)值)分别为8.52和9.77μg/mL;化合物3c-08对茶叶炭疽病菌和茶叶轮斑病菌的EC_(50)值分别为9.17和8.83μg/mL,具有在茶叶病害防治方面应用的潜力.与先导化合物血根碱盐酸盐相比,多数目标化合物表现出较优的抑菌活性.杀虫活性初步测定结果表明,在400μg/mL浓度下该类化合物对桃蚜的杀虫活性一般.本文为血根碱衍生物的进一步开发利用提供了一定依据.

Synthesis,insecticidal activities,and SAR studies of novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives

Diamide compounds such as chlorantraniliprole,a famous anthranilic diamide insecticide targeting the insect ryanodine receptor(Ry R),have received continuous attention in pesticide research during the past 15 years owing to their excellent insecticidal potentials.With the aim of discovering new heterocyclic pesticides used for crop protection,based on the structural information of compound M from the reported pharmacophore-based virtual screening for Ry R insecticides and diamide compound,a series of new heterocyclic mono-,di-,and tri-amide derivatives containing piperazine moiety have been synthesized in this paper.The new compounds were identified and confirmed by melting point,^(1)H NMR,^(13)C NMR and HRMS.Compound M was firstly validated for insecticidal activities,and the new synthesized compounds were all made comprehensive insecticidal evaluations against diamondback moth and oriental armyworm.The bioassay results showed that some of the compounds exhibit favorable insecticidal potentials,particularly some novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives such as 8 g,14 a,15 a,15 g,15 i,15 j,15 k,15 l,and 15 m could be used as new insecticidal leading structures for further study(e.g.,towards diamondback moth,15i-15 m LC_(50):0.0022-0.0081 mg/L).The structure-activity relationships of the compounds discussed in detail provide useful guidance for further design and development of new insecticides.

Synthesis, insecticidal activities and DFT study of pyrimidin-4-amine derivatives containing the 1,2,4-oxadiazole motif

Twenty six novel pyrimidin-4-amine derivatives containing the 1,2,4-oxadiazole motif were synthesized. Their chemical structures were confirmed by ^(1)H nuclear magnetic resonance (NMR), ^(13)C NMR, and high-resolution mass spectrography. The insecticidal activity results indicated that some of them possessed excellent insecticidal activity (100%) against Mythimna separate, especially for compounds 6d, 6f, 6o, 6w, 6y and 6z. These compounds exhibited no activity against the insects Aphis medicagini and Tetranychus cinnabarinus. The structure- insecticidal activity relationships are discussed. Density functional theory analysis can potentially be used to design more active compounds. These results provide useful insecticide design information for further optimization.

应用多维标度法预测硝基苯化合物的生物毒性

将6种基团参数用于硝基苯化合物取代基结构参数化,应用林知己夫多维标度法,从一组对象之间的相似性度量或非相似性度量出发,求出这组对象在某低维空间中的标度对它们进行了定量构效关系研究,同时将所得的结果映射到二维空间以得到更直观的图像.研究结果表明,该方法能将样本数分成明显的高活性区、中活性区及低活性区三个部分,与实验结果完全吻合.