Bioactive Neolignans from the Leaves of Piper rivinoides Kunth (Piperaceae)

Piper rivinoides is a Brazilian Piperaceae species of a little research from a chemical and biological point of view. The crude hydroalcoholic extract from leaves, the n-hexane fraction and pure isolated compounds from the leaves were evaluated against two strains of Candida albicans as well as Leishmania amazonensis and L. chagasi. Bioguided purification of the n-hexane fraction lead to isolation and chemical characterization of a mixture of two benzofuran neolignans, 2-(4’-methoxyphenyl)-3-methyl-5-(E)-propenylbenzofuran (1) and eupomatenoid-3 (2) as well as the pure compounds: eupomatenoid-5 (3), (2R,3R)-2,3-dihydro-2-(4’-hydroxy-3’-methoxyphenyl)-3-methyl-5(E)-propenylbenzofuran (4), eupomatenoid-6 (5) and conocarpan (6). The first approach in quantification found with basis on quantitative nuclear magnetic resonance showed that the n-hexane fraction contains about 29.8% of eupomatenoid-5 (3), 7.6% of eupomatenoid-6 (5) and 5.5% of conocarpan (6). The biological results showed conocarpan as the most active compound with less cytotoxicity than the other tested compounds. Our results suggest conocarpan as owner of the best scaffold model of the four neolignans tested for new promising antimicrobial agents against the tested parasites. The high content of neolignans in the n-hexane fraction stands out P. rivinoides as an important source of bioactive neolignans.