Abstract
A new series of piperazine-derived compounds were synthesized and evaluated as HIV-1 reverse transcriptase (HIV-1 RT) inhibitors. Flexibility of the piperazine structure plays an importance role for its diverse pharmacological properties and medicinal potentialities. Compounds having better inhibitory activities against HIV-1 RT were tested for their anti-HIV activity in TZM-bl cell line. Among tested compounds, 9k exhibited better anti-HIV activity with an IC50 value of 13.18 ± 1.62 μg/ml and a therapeutic index value of 2.26 in TZM-bl cell line. Furthermore, molecular docking analysis revealed the similar binding modes of 9k and delavirdine with HIV-1 RT in which carbonyl group of 9k established hydrogen bonding with Lys103 residue as delavirdine, and other hydrophobic groups were stabilized with hydrophobic area (TRP229, LEU100, TYR188, PHE227, VAL106, PRO236, TYR181, TYR188, TRP229, and TYR318 residues) of HIV-1 RT. Present study suggests that compound 9k may serve as a new lead template for further modification to obtain therapeutically useful molecule for the treatment of HIV infection.
