Docking Studies on the Effect of β-Ring Expansion in Binding of TIBO Derivatives to HIV-1 Reverse Transcriptase

Designing of new inhibitors to human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT) is one of the important research area in AIDS therapies. Non-nucleoside inhibitors of reverse transcriptase (NNIRT) are attractive drug candidates for their unique binding site to the reverse HIV-1 RT and less adverse side effects. The effect of expansion of diazepine ring from seven to eight in some tetrahydroimidazo [4,5,1-jk][1,4]benzodiazepin-2(1H)-thione (TIBO) derivatives as NNIRT has been investigated by docking procedure. Sixteen conventional TIBO derivatives with known HIV-1 RT inhibitor activity were selected and their β-ring was expanded to eight. The three-dimensional (3D) geometry of the molecules was optimized by AM1 semiempirical method and then interacted with the HIV-1 RT enzyme using Autodock program. Twelve out of sixteen of the new molecules were docked into the enzyme. The resulted free energies of docking indicated that the newly proposed molecules bond to the enzyme with comparable tendency in relative to their corresponding conventional homologous. It was found that three new compounds bind to the receptor stronger than that of their corresponding 7-membered ring derivatives and can be considered as new candidate for synthesis