标题：Evaluation of the inhibitory effect of caffeic acid and gallic acid on tetR and tetM efflux pumps mediating tetracycline resistance in Streptococcus sp., using computational approach
摘要：AbstractBackgroundEmergence oftet-efflux pump based tetracycline resistance inStreptococcusspp. is quite alarming worldwide posing a serious impediment in the treatment process. This leads to the search of novel target proteins to develop newer drugs against tetracycline resistantStreptococcispp. Caffeic acid and gallic acid being vital phenolic compounds might target thetetbased efflux pumps. The aim of the present study is thus to explore the inhibitory potential of caffeic acid and gallic acid againsttet-efflux pump mediated tetracycline resistantStreptococcispp.Materials and methods3D structure oftetR and tetMwas retrieved from the PDB data bank with further optimization of both the protein and ligands.In-silicoinhibitory potential of the selected ligands againsttetR and tetMwas done by AutoDock 2.0 and was visualized with Accelrys Discovery Studio Visualizer tool with the assessment of the molecular properties of the ligands by molinspiration calculations and further assessment for their drug likeliness.ResultsCaffeic acid seem to possess promising inhibitory activity to targettetR and tetMwith a promising binding energy of –5.93 and −4.6 Kcal/mol with 7 and 6 hydrogen bonds respectively. Molinspiration assessments showed zero violations with TPSA values < 140 Å towards the best oral bioavailability.ConclusionThe findings of the study emphasize that caffeic acid and gallic acid to possess a promising inhibitory effect againsttetR and tetMofStreptococcispp. suggesting caffeic acid and gallic acid as the best drug candidates to combattet-pump mediated tetracycline resistance with furtherin-vivovalidation targeting the same.
