Drug resistance reversal potential of multifunctional thieno[3,2-c]pyran via potentiation of antibiotics in MDR P. aeruginosa
Gaurav Raj Dwivedi, Reeta Rai, Ramendra Pratap, Khusbu Singh, Sanghamitra Pati, Satya Narayan Sahu, Rajni Kant, Mahendra P. Darokar, Dharmendra Kumar Yadav
Abstract
We explored the antibacterial potential (alone and combination) against multidrug resistant (MDR) Pseudomonas aeruginosa isolates KG-P2 using synthesized thieno[3,2-c]pyran-2-ones in combination with different antibiotics. Out of 14 compounds, two compounds (3g and 3l) abridged the MIC of tetracycline (TET) by 16 folds. Compounds was killing the KG-P2 cells, in time dependent manner, lengthened post-antibiotic effect (PAE) of TET and found decreased the mutant prevention concentration (MPC) of TET. In ethidium bromide efflux experiment, two compounds repressed the drug transporter (efflux pumps) which is further supported by molecular docking of these compounds with efflux complex MexAB-OprM. In another study, these compounds inhibited the synthesis of biofilm.