Design of gossypetin derivatives based on naturally occurring flavonoid in Hibiscus sabdariffa and the molecular docking as antibacterial agents

Objectives This study was purposed to design gossypetin derivatives which have higher activity than the parent compound found in Hibiscus sabdariffa and to find the most potent compound as the antibacterial agent. Methods Twenty-five gossypetin derivatives were designed by conjugation the molecular structure of gossypetin with acyl group from some natural phenolic acids. The antibacterial activity was predicted by docking simulation on Escherischia coli DNA gyrase (PDB. 1KZN) which was performed by Molegro Virtual Docker. Potency as an antibacterial agent was evaluated based on binding affinity, hydrogen bond, and similarity of binding pattern with reference ligand Clorobiocin. Results Almost all derivatives showed higher binding affinity than gossypetin (docking score -113.43 kcal/mol). The most active compound was 3G19 with docking score -167.42 kcal/mol which was comparable to clorobiocin (docking score -167.75 kcal/mol). The compounds displaying higher activity than gossypetin were belonged to 7,4'-dimethyl and 3,7,4'-trimethylgossypetin of coumaric acid, caffeic acid, and also ferulic acid. The compounds showed similar binding mode with clorobiocin especially in interaction with Asn46. Conclusions Gossypetin derivatives designed by conjugating the gossypetin with phenolic acyl increased in silico antibacterial activity of the parent compound. The 3,7,4'-trimethylgossypetin of coumaric acid was selected as the most potent compound for antibacterial agents.