One-Pot Green Synthesis and Biological Evaluation of Dimedone-Coupled 2,3-Dihydrofuran Derivatives to Divulge Their Inhibition Potential against Staphylococcal Thioredoxin Reductase Enzyme

  • ACS Omega. 2024 Oct 21;9(43):43414-43425. doi: 10.1021/acsomega.4c04325.
Manjari Shukla  1 ,  Ghanshyam Mali  2 ,  Supriya Sharma  2 ,  Sushobhan Maji  1 ,  Vinay Kumar Yadav  1 ,  Amit Mishra  1 ,  Rohan D Erande  2 ,  Sudipta Bhattacharyya  1
Affiliations
  • 1. Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur 342037, Rajasthan, India.
  • 2. Department of Chemistry, Indian Institute of Technology, Jodhpur 342037, Rajasthan, India.
PMID: 39494007 DOI: 10.1021/acsomega.4c04325
Abstract

New therapeutic leads are in global demand against multiple drug-resistant Staphylococcus aureus, as presently there is no drug of choice left to treat this pathogen. In the present work, we have designed, synthesized, and in vitro validated dimedone-coupled 2,3-dihydrofuran (DDHF)-based inhibitor scaffolds against Staphylococcal thioredoxin reductase (SaTR), a pivotal drug target enzyme of Gram-positive pathogens. Accordingly, a green multicomponent method that is both efficient and one pot has been optimized to synthesize DDHF derivatives. The synthesized DDHF derivatives were found to inhibit a purified SaTR enzyme. The best inhibitor derivative, DDHF20, inhibits SaTR as a competitive inhibitor for the NADPH binding site at low micromolar concentrations. DDHF20-capped silver nanoparticles are synthesized and characterized, and their bactericidal property has been checked in vitro. Furthermore, detailed in silico-based structure-guided functional studies have been carried out to uncover the plausible mode of action of DDHF20 as a potential anti-Staphylococcal therapeutic lead.

Products