Oxazolidines from Neocalyptrocalyx Longifolium Inhibit MsrA Protein in Methicillin Resistant Staphylococcus Aureus

Thalisson Amorim de Souza,Joanda Paola Raimundo Silva，Josean Fechine Tavares,Marcelo Sobral da Silva

REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY（2023）

Universidade Federal da Paraíba | Universidade Estadual da Paraíba | Universidade Federal Fluminense

Cited 1|Views21

Abstract

The emergence of antimicrobial resistance has generated global concerns regarding many pathogenic microorganisms, such as methicillin-resistant Staphylococcus aureus. The inhibition of microbial molecular targets by natural products has led to the discovery of new paths capable of reverting resistance to classical antimicrobial agents. Neocalyptrocalyx longifolium (Mart.) Cornejo Iltis, Capparaceae, is a Brazilian medicinal plant indicated for the treatment of skin and respiratory tract bacterial infections. Nevertheless, few studies have investigated its chemical composition. In view of the current development of pathogenic microorganism resistance, the isolation and identification of efflux pumps inhibitors from the roots of N. longifolium is described herein. In addition, the elements that contribute to substrate binding and inhibition of the MsrA protein, an ABC-type transporter, were analyzed based on in silico experiments. Five substances were isolated and characterized by NMR and HRMS. Four of them exhibited interesting structural features, composed of 1,3-oxazolidine-2-thione and 1,3-oxazolidine-2-one cores. 5-Methyl-5-ethyl-oxazolidine-2-one, an undescribed natural product, inhibited the activity of the MsrA transporter and, therefore, the potency of erythromycin was increased. Docking analysis revealed specific hydrogen interactions for this inhibitor at the MsrA ATP binding site.

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Key words

Antimicrobial resistance,Caatinga,Erythromycin,Modulatory activity,Multidrug resistance,Oxazolidinone

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