title: Quantitative structure-activity relationships and comparative molecular field analysis of TIBO derivatised HIV-1 reverse transcriptase inhibitors.
abstract: Quantitative structure-activity relationships (QSAR) and Comparative Molecular Field Analysis (CoMFA) have been applied in order to explain the structural requirements of HIV-1 reverse transcriptase (HIV-1 RT) inhibitory activity of TIBO derivatives on the MT-4 cells. The best QSAR model is satisfactory in both statistical significance and predictive ability. The derived structural descriptors indicate the importance of electronic contributions toward the HIV-1 RT inhibition of this class of compounds. However, it could not reveal any hydrophobic influence because of high collinearity between C2 and log P variables. In order to cope with steric interaction in the correlation, 3D-QSAR was performed using CoMFA. The obtained CoMFA model shows high predictive ability, rcv2 = 0.771, and clearly demonstrates its potential in the steric feature of the molecules through contour maps, explaining a majority (81.8%) of the variance in the data. Consequently, these results can be useful in identifying the structural requirements of TIBO derivatives and helpful for better understanding the HIV-1 RT inhibition. Eventually, they provide a beneficial basis to design new and more potent inhibitors of HIV-1 RT.
authors.affiliation: Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand. fscisph@ku.ac.th
authors.forename: S
authors.initials: S
authors.lastname: Hannongbua
authors.forename: P
authors.initials: P
authors.lastname: Pungpo
authors.forename: J
authors.initials: J
authors.lastname: Limtrakul
authors.forename: P
authors.initials: P
authors.lastname: Wolschann
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry* / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000187:drug effects; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines; C092133:R 79882; D054303:HIV Reverse Transcriptase