Oxazolidine Compounds from Neocalytrocalyx Longifolium (capparaceae) and Their Activity As Msra (ABC) Efflux Pump Inhibitors: an in Vitro and in Silico Approach

The absence of novel antibiotics associated with the emergence of antimicrobial resistance has generated global concerns regarding many pathogenic microorganisms (PMs), such as methicillin-resistant Staphylococcus aureus (MRSA). The inhibition of efflux pumps (EFPs) by natural products has led to the discovery of new paths capable of reverting resistance to classical antimicrobial agents. Neocalyptrocalyx longifolium is a Brazilian medicinal plant indicated for the treatment of inflammation and bacterial infections of the skin and respiratory tract. Nevertheless, few studies have investigated this plant’s chemical composition. In view of current PM resistance, we report the isolation and spectroscopic identification of EFP inhibitors from the roots of N. longifolium . In addition, the elements that contribute to substrate binding and inhibition of the MsrA (ABC) EFP were analyzed based on in silico experiments. Five substances were isolated and characterized by 1 H and 13 C nuclear magnetic resonance (NMR); four of them exhibited interesting structural features, composed of 1,3-oxazolidine-2-thione and two 1,3-oxazolidine-2-one cores. Compound 2 (5-ethyl-5-methyl-oxazolidine-2-one) inhibited the MsrA pump and increased the potency of erythromycin. Docking analysis revealed specific hydrogen interactions in the MsrA protein ATP binding site. The 5 substances are reported for the first time in the plant studied. These results contribute to consolidating the current knowledge regarding the chemical composition of the Neocalyptrocalyx genus and the biological activities of 2-oxazolidinone derivatives.