Synthesis, structure–activity relationship and molecular docking of cyclohexenone based analogous as potent non-nucleoside reverse-transcriptase inhibitors

•A convenient route for the synthesis of eight new cyclohexenone derivatives from Robinson annulation is described.•Micro- and spectral analysis have been effectively operated to confirm the molecular structures of cyclohexenones.•These cyclohexenones displayed potential activity against reverse transcriptase.•The docking protocol and bioassay studies of as-synthesized cyclohexenones are in good agreement.

The chalcones core in compounds is advantageously chosen effective synthons, which offer exciting perspectives in biological and pharmacological research. The present study reports the successful development of eight new cyclohexenone based anti-reverse transcriptase analogous using rational drug design synthesis principles. These new cyclohexenone derivatives (CDs) were synthesized by following a convenient route of Robinson annulation, and the molecular structure of these CDs were later confirmed by various analytical techniques such as 1H NMR, 13C NMR, FT-IR, UV–Vis spectroscopy and mass spectrometry. All the synthesized compounds were screened theoretically and experimentally against reverse transcriptase (RT) and found potentially active reverse transcriptase (RT) inhibitors. Of the compounds studied, the compound 2FC4 showed high interaction with RT at non-nucleoside binding site, contributing high free binding energy (ΔG −8.01 Kcal) and IC50 (0.207 μg/ml), respectively. Further results revealed that the compounds bearing more halogen groups, with additional hydrophobic character, offered superior anti-reverse transcriptase activity as compared to rest of compounds. It is anticipate that the present study would be very useful for the selection of potential reverse transcriptase inhibitors featuring inclusive pharmacological profiles.

Graphical abstractOn the basis of rational drug design synthesis principles eight novel and potential cyclohexenone based anti-reverse transcriptase analogous have been successfully synthesized and evaluated in detail.Figure optionsDownload full-size imageDownload as PowerPoint slide