Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses.
Thiocarbamates (TCs) have been recently identified as a new class of potent non-nucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses, has been used to elucidate the atomic details of the RT/TC interactions and to identify the most important features impacting the TC antiretroviral activity. The CoMFA model resulted to be the more predictive, and gave r(2)=0.93, r(cv)(2)=0.53, SEE=0.292, F=180, and r(test)(2)=0.70. The 3D-QSAR field contributions and the structural features of the RT binding site showed a good correlation. These studies will be useful to design new TCs with improved potency also against clinically relevant resistant mutants.
Cichero
Elena
E
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV n.3, 16132 - Genova. Italy.
Cesarini
Sara
S
Fossa
Paola
P
Spallarossa
Andrea
A
Mosti
Luisa
L
D003198:Computer Simulation; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011485:Protein Binding; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology*
D018894:Reverse Transcriptase Inhibitors; D013859:Thiocarbamates; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase