Quantitative structure-activity relationship studies on 1-aryl-tetrahydroisoquinoline analogs as active anti-HIV agents.
Predictive quantitative structure-activity relationship analysis was developed for a diverse series of recently synthesized 1-aryl-tetrahydroisoquinoline analogs with anti-HIV activities in this study. The conventional 2D-QSAR models were developed by genetic function approximation (GFA) and stepwise multiple linear regression (MLR) with acceptable explanation of 94.9% and 95.5% and good predicted power of 91.7% and 91.7%, respectively. The results of the 2D-QSAR models were further compared with 3D-QSAR model generated by molecular field analysis (MFA), investigating the substitutional requirements for the favorable receptor-drug interaction and quantitatively indicating the important regions of molecules for their activities. The results obtained by combining these methodologies give insights into the key features for designing more potent analogs against HIV.
College of Chemical Engineering and Materials Science, Zhejiang University of Technology, 18, Chaowang Road, Hangzhou, Zhejiang 310014, China.
Ke-xian
KX
Chen
Hai-ying
HY
Xie
Zu-guang
ZG
Li
Jian-rong
JR
Gao
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D044005:Tetrahydroisoquinolines; D054303:HIV Reverse Transcriptase