探讨扎那米韦类衍生物对禽流感病毒神经氨酸酶(NA)的抑制作用,为新的NA抑制剂的研发和设计提供有用的结构信息,进而对流感病毒的新药研发产生一定的积极意义.首先,选取22个扎那米韦类的合成化合物为配体,与PDB(protein data bank)数据...探讨扎那米韦类衍生物对禽流感病毒神经氨酸酶(NA)的抑制作用,为新的NA抑制剂的研发和设计提供有用的结构信息,进而对流感病毒的新药研发产生一定的积极意义.首先,选取22个扎那米韦类的合成化合物为配体,与PDB(protein data bank)数据库中下载的3BEQ受体蛋白进行对接.然后,采用CoMFA和CoMSIA方法建立3D-QSAR预测模型,其中,CoMFA和CoMSIA模型的交叉验证系数q^(2)分别为0.599和0.592,非交互验证相关系数R^(2)分别为0.999和0.775,这一结果表明2种模型都具有良好的预测能力.最后,根据对接结果和3D-QSAR模型的预测分析,设计得到2种对禽流感病毒抑制活性更高的分子.展开更多
使用比较分子力场分析法(CoMFA)和比较分子相似性指数法(CoMSIA)对33个已报道的喹啉酮类BRD4抑制剂进行3D-QSAR模型建立,研究了其化学结构和生物活性间的关系,并用计算机辅助药物设计(computer-aided drug design,CADD)设计出7个喹啉酮...使用比较分子力场分析法(CoMFA)和比较分子相似性指数法(CoMSIA)对33个已报道的喹啉酮类BRD4抑制剂进行3D-QSAR模型建立,研究了其化学结构和生物活性间的关系,并用计算机辅助药物设计(computer-aided drug design,CADD)设计出7个喹啉酮类抑制剂。结果表明,建立的CoMFA(q^(2)=0.926,r^(2)=0.997,r^(2)_(pred)=0.744)和CoMSIA(q^(2)=0.939,r^(2)=0.991,r^(2)_(pred)=0.786)模型具有较好的预测能力,基于这些模型设计的7个新喹啉酮类BRD4抑制剂具有高活性,并对其进行ADMET性质评价和类药性分析。以上研究结果有助于改造和开发更加有效的喹啉酮类BRD4抑制剂。展开更多
In search of natural renewable resource-based bioactive molecules,20 hydroxamate inhibitors were designed and synthesized using cinamaldehyde as the starting material.Their structures were characterized by FT-IR,^(1)H...In search of natural renewable resource-based bioactive molecules,20 hydroxamate inhibitors were designed and synthesized using cinamaldehyde as the starting material.Their structures were characterized by FT-IR,^(1)HNMR,^(13)C NMR,and HRMS.And in vitro antifungal activity of the target compounds against 8 tested fungi was preliminarily evaluated by the agar dilution method.The bioassay results revealed that at the concentration of 50 mg/L,the target compounds exhibited certain inhibitory activity against 8 tested fungi,in which compounds 5r(R=o,o-Cl),5c(R=m-F),5b(R=o-F)and 5p(R=o,p-Cl)displayed better inhibitory activity of 93.3%,76.8%,75.3%and 72.3%,respectively,against P.piricola than that of the positive control chlorothalonil.At the same time,3D-quantitative structure-activity relationship(3D-QSAR)study was carried out to explore the relationship of the molecular structures with their antifungal activity against P.piricola.And a reasonable and effective 3D-QSAR model(r^(2)=0.980,q^(2)=0.501)has been established.Besides,molecular docking was also performed to reveal the binding mode of the target compound 5r(R=o,o-Cl)with succinate dehydrogenase(SDH).It was found that compound 5r could be well embedded in the active pocket of the receptor protein.This showed a similar mode with SDH inhibitors(SDHI)carboxin.展开更多
文摘探讨扎那米韦类衍生物对禽流感病毒神经氨酸酶(NA)的抑制作用,为新的NA抑制剂的研发和设计提供有用的结构信息,进而对流感病毒的新药研发产生一定的积极意义.首先,选取22个扎那米韦类的合成化合物为配体,与PDB(protein data bank)数据库中下载的3BEQ受体蛋白进行对接.然后,采用CoMFA和CoMSIA方法建立3D-QSAR预测模型,其中,CoMFA和CoMSIA模型的交叉验证系数q^(2)分别为0.599和0.592,非交互验证相关系数R^(2)分别为0.999和0.775,这一结果表明2种模型都具有良好的预测能力.最后,根据对接结果和3D-QSAR模型的预测分析,设计得到2种对禽流感病毒抑制活性更高的分子.
文摘使用比较分子力场分析法(CoMFA)和比较分子相似性指数法(CoMSIA)对33个已报道的喹啉酮类BRD4抑制剂进行3D-QSAR模型建立,研究了其化学结构和生物活性间的关系,并用计算机辅助药物设计(computer-aided drug design,CADD)设计出7个喹啉酮类抑制剂。结果表明,建立的CoMFA(q^(2)=0.926,r^(2)=0.997,r^(2)_(pred)=0.744)和CoMSIA(q^(2)=0.939,r^(2)=0.991,r^(2)_(pred)=0.786)模型具有较好的预测能力,基于这些模型设计的7个新喹啉酮类BRD4抑制剂具有高活性,并对其进行ADMET性质评价和类药性分析。以上研究结果有助于改造和开发更加有效的喹啉酮类BRD4抑制剂。
文摘In search of natural renewable resource-based bioactive molecules,20 hydroxamate inhibitors were designed and synthesized using cinamaldehyde as the starting material.Their structures were characterized by FT-IR,^(1)HNMR,^(13)C NMR,and HRMS.And in vitro antifungal activity of the target compounds against 8 tested fungi was preliminarily evaluated by the agar dilution method.The bioassay results revealed that at the concentration of 50 mg/L,the target compounds exhibited certain inhibitory activity against 8 tested fungi,in which compounds 5r(R=o,o-Cl),5c(R=m-F),5b(R=o-F)and 5p(R=o,p-Cl)displayed better inhibitory activity of 93.3%,76.8%,75.3%and 72.3%,respectively,against P.piricola than that of the positive control chlorothalonil.At the same time,3D-quantitative structure-activity relationship(3D-QSAR)study was carried out to explore the relationship of the molecular structures with their antifungal activity against P.piricola.And a reasonable and effective 3D-QSAR model(r^(2)=0.980,q^(2)=0.501)has been established.Besides,molecular docking was also performed to reveal the binding mode of the target compound 5r(R=o,o-Cl)with succinate dehydrogenase(SDH).It was found that compound 5r could be well embedded in the active pocket of the receptor protein.This showed a similar mode with SDH inhibitors(SDHI)carboxin.
