ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Identification of recently FDA-approved drugs as a repurposing candidate against multidrug efflux pump subunit AcrB of Escherichia coli: a molecular docking, MM/GBSA, molecular dynamics approach

Debanjan Dey and Anoop Kumar

Evidence Based Research Lab (EBR 106), Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR),, Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi, India

E-mail: abitmesra@gmail.com

Received: 14 October 2024  Accepted: 13 August 2025

Abstract:

Clinical treatment for infections and illnesses caused by multidrug-resistant bacteria is still lacking. Efflux pumps serve as one of the key mechanisms for bacteria to resist antibiotics, facilitating the transfer of antibiotics from the interior of their cells to the external surroundings. Inhibiting these pumps could be an intriguing approach to regaining antibiotic efficacy in multi-drug resistance (MDR) bacterial infections. The ongoing study endeavors to identify recently FDA-approved drugs that could be repurposed as good candidates against the AcrB subunit of Escherichia coli's multidrug efflux pump. Through the utilization of structure-guided approaches, this study was conducted using the AcrB subunit (PDB: 7B8S) to elucidate the inhibitory effects of selected FDA-approved drugs, using techniques such as molecular docking, MM/GBSA, and molecular dynamics. Among 202, 78 drugs underwent scrutiny for their interaction with the AcrB protein and 3 drugs demonstrated superior binding conformations (dock score: ≥ − 8.0) marked by favorable energetic profiles within the target's active site which were subsequently subjected to 200-ns molecular dynamics (MD) simulation. The molecular docking results have shown favored binding conformation of 3 drugs in the active site of the efflux pump of Gram-negative bacteria. The molecular dynamics studies results have shown the stability of tenapanor, lumateperone tosylate, and lasmiditan in the active site of the AcrB protein of E. coli. The identified drugs can be repurposed against resistant bacterial infections through the inhibition of efflux pumps with further experimental validation.

Graphical Abstract

Keywords: US-FDA-approved drugs; Efflux pump; Molecular docking; Molecular dynamics

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04316-w

Chemical Papers 79 (11) 8161–8189 (2025)