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 K Yadav

doi:10.1016/j.biopha.2021.112084

Drug resistance reversal potential of multifunctional thieno[3,2-c]pyran via potentiation of antibiotics in MDR P. aeruginosa

Biomed Pharmacother. 2021 Oct:142:112084. doi: 10.1016/j.biopha.2021.112084. Epub 2021 Aug 24.

Authors

Gaurav Raj Dwivedi¹, Reeta Rai², Ramendra Pratap³, Khusbu Singh⁴, Sanghamitra Pati⁴, Satya Narayan Sahu⁵, Rajni Kant⁶, Mahendra P Darokar⁷, Dharmendra K Yadav⁸

Affiliations

¹ Microbiology Department, ICMR-Regional Medical Research Centre, BRD Medical College Campus, Gorakhpur 273013, India. Electronic address: grdnikhil@gmail.com.
² Department of Biochemistry, AIIMS Ansari Nagar, New Delhi 110029, India.
³ Department of Chemistry, North campus University of Delhi, Delhi 110007, India. Electronic address: rpratap@chemistry.du.ac.in.
⁴ Microbiology Department, ICMR-Regional Medical Research Centre, Bhubaneshwar 751023, Odisha, India.
⁵ Government College Balrampur, Balrampur-Ramanujganj, Chhattisgarh 497119, India.
⁶ Microbiology Department, ICMR-Regional Medical Research Centre, BRD Medical College Campus, Gorakhpur 273013, India.
⁷ Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, ̥Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow 226015, India.
⁸ Gachon Institute of Pharmaceutical Science and Department of Pharmacy, College of Pharmacy, Gachon University, 191 Hambakmoeiro, Yeonsu-gu, Incheon 21924, Republic of Korea. Electronic address: dharmendra30oct@gmail.com.

PMID: 34449308
DOI: 10.1016/j.biopha.2021.112084

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.

Keywords: 2-c]pyran-2-ones; Biofilm synthesis; Drug resistance reversal; Efflux pump inhibition; Synthetic compounds; Thieno[3.

Publication types

Comparative Study

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Biofilms / drug effects
Drug Resistance, Multiple, Bacterial
Drug Synergism
Drug Therapy, Combination
Microbial Sensitivity Tests
Molecular Docking Simulation
Pseudomonas aeruginosa / drug effects*
Pyrones / chemical synthesis
Pyrones / chemistry
Pyrones / pharmacology*
Structure-Activity Relationship
Tetracycline / pharmacology
Time Factors

Substances

Anti-Bacterial Agents
Pyrones
Tetracycline