Binding interaction of potent HIV-1 NNRTIs, amino-oxy-diarylquinoline with the transport protein using spectroscopic and molecular docking.

In the present investigation, the intermolecular interaction of 4-(4'-cyanophenoxy)-2-(4''-cyanophenyl)-aminoquinoline (1), a potent non-nucleoside HIV-1 reverse transcriptase inhibitors, with the transport proteins, namely bovine serum albumin (BSA) and human serum albumin (HSA), has been investigated under physiological conditions employing UV-Vis, fluorescence spectrophotometry, competitive binding experiments and molecular docking methods. The results indicated that binding of (1) to the transport proteins caused fluorescence quenching though a static quenching mechanism. The number of binding site (n) and the apparent binding constant (K) between (1) and the transport proteins were determined to be about 1 and 10-10 L·mol (at three different temperatures; 298, 308, 318 K), respectively.

Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors.

In this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT.