Computer-aided design of potential anti-HIV-1 non-nucleoside reverse transcriptase inhibitors by contraction of β-ring in TIBO derivatives

TIBO derivatives, as non-nucleoside reverse transcriptase inhibitors, have gained a definitive place in the treatment of HIV-1 infections. Some new TIBO-like derivatives have been designed by contraction of the β-ring (diazepine ring) of TIBO derivatives from seven to 6-membered ring. The autodock program was used to study the binding of the molecules to HIV-1 the reverse transcriptase enzyme. A total of 16 TIBO derivatives were examined. The results showed that both the 7 and 6-membered ring compounds could dock into the enzyme. A linear relationship was obtained between the total free energy of docking and pIC50 of the conventional TIBO derivatives. The total free energy of docking indicated that some of these derivatives were bonded to the receptor stronger than the 7-membered derivatives. Meanwhile, in comparison with 8-Cl TIBO molecule, which is currently used in the HIV treatment, one 6-membered ring derivative showed more binding affinity toward the reverse transcriptase enzyme.