Anti-Mycobacterium tuberculosis activity of eupomatenoid-5 from Piper regnellii

Tuberculosis (TB) is a disease caused mainly by Mycobacterium tuberculosis, which has been widespread since ancient times and remains an important public-health problem, especially in developing countries. One worrying factor in TB treatment is the prevalence of drug-resistant strains, and hence there is an urgent need to develop new anti-TB drugs. The interest in natural products, especially the search for new active principles, has stimulated to invest in studies involving plants. Piper regnelli var. pallescens is popularly known as caapeba or pariparoba in Brazil. The leaves and roots are used as extracts, infusions or plasters to treat wounds, swellings and infections. The present study determined the anti-M. tuberculosis activity and cytotoxicity of eupomatenoid-5. The extraction by supercritical fluid (SFE-CO₂) from leaves of Piper regnellii var. pallescens was conducted at a temperature of 60 °C and pressure of 24.4 MPa. The chromatographic column purification afforded the isolation of the neolignan eupomatenoid-5, which was identified by ¹H NMR and comparison with literature data. Anti-M. tuberculosis activity was evaluated using a resazurin microtiter assay plate (REMA) to determine the MIC. The cytotoxicity assay was carried out in macrophages J774G.8 by sulforhodamine B colorimetric assay. Anti-M. tuberculosis activity of eupomatenoid-5 and the cytotoxicity exhibited very good activity (MIC of 1.9 µg/mL) and selectivity index (SI = 20). Eupomatenoid-5 is a potential compound for future investigations in anti-TB drugs development. Further studies are being conducted to understand the mechanism of action of this promising compound as well as the synergistic activity with conventional treatment.