A Structure Activity Relationship Study of 3,4'-dimethoxyflavone for ArlRS Inhibition in

Overview

Journal Org Biomol Chem

Publisher Royal Society of Chemistry

Specialties Biochemistry
Chemistry

Date 2023 Apr 4

PMID 37013457

Authors

Alexander W Weig

Patrick M OConner

Jakub M Kwiecinski

Orry M Marciano

Angelica Nunag

Andrew T Gutierrez

Roberta J Melander

Alexander R Horswill

Christian Melander

Affiliations

Soon will be listed here.

Abstract

Infections caused by methicillin-resistant (MRSA) are difficult to treat due to their resistance to many β-lactam antibiotics, and their highly coordinated excretion of virulence factors. One way in which MRSA accomplishes this is by responding to environmental stimuli using two-component systems (TCS). The ArlRS TCS has been identified as having a key role in regulating virulence in both systemic and local infections caused by . We recently disclosed 3,4'-dimethoxyflavone as a selective ArlRS inhibitor. In this study we explore the structure-activity relationship (SAR) of the flavone scaffold for ArlRS inhibition and identify several compounds with increased activity compared to the parent. Additionally, we identify a compound that suppresses oxacillin resistance in MRSA, and begin to probe the mechanism of action behind this activity.

Citing Articles

Structure-Photoreactivity Relationship Study of Substituted 3-Hydroxyflavones and 3-Hydroxyflavothiones for Improving Carbon Monoxide Photorelease.

Jezequel Y, Sverak F, Ramundo A, Orel V, Martinek M, Klan P J Org Chem. 2024; 89(7):4888-4903.

PMID: 38517741 PMC: 11002828. DOI: 10.1021/acs.joc.4c00070.

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