Medicinal Chemistry, Drug Discovery & Drug Delivery

Biography

Biography: Ziyuan Zhou

Abstract

Antimicrobial resistance (AMR) is gravely threatening modern health care system. The traditional antimicrobials themselves are the catalyst for AMR. Thus, novel antimicrobial strategies are desperately needed. The targeting of bacterial RecA represents an alternative approach to combat AMR, as RecA inhibitors could block RecA mediated SOS response, while not inhibit bacteria growth, presumably impose less selective pressure for AMR. A series of naphthalene polysulfonated compounds, represented by suramin, were reported to be RecA inhibitors. However, the specific interaction between these compounds and RecA is still unclear. We identified the binding site on RecA and predict the binding details of the naphthalene polysulfonated compounds with RecA by multiple theoretical approaches. Taken together, this work dedicates to correlate the inhibitor-RecA interactions and inhibitory activities at the molecular level, and to provide theoretical and experimental foundations for the screening of novel compounds as RecA targeting antibiotic adjuvants. We have elucidated a proposed molecular interaction mechanism for the previously observed, but molecularly uncharacterized naphthalene polysulfonated compounds as the bacterial RecA inhibitors. These computational and experimental results suggest this scaffold design is a promising strategy for the developing novel compounds with improved adjuvants against RecA proteins from a broad spectrum of bacterial pathogens. Conclusions of this work can be included in a drug discovery pipeline as a way to optimize drug leads and increase the successful rate in the future RecA targeting inhibitors discovery.