Atividade antimalárica in vitro de extratos e metabólitos naturais da Simaba pubicarpa (Simaroubaceae) e galatos de alquila sintéticos

Abstract

Reports of resistance of Plasmodium falciparum to artemisinin and artemisinin-based combination therapies (ACTs) have raised significant concern within the medical and scientific communities, highlighting the urgent need to identify new chemical entities with antiplasmodial activity. The genus Simaba (Simaroubaceae) is known for its diversity of secondary metabolites with potential antimalarial properties. Simaba pubicarpa, a recently described tree species found in the Adolpho Ducke Forest Reserve, Manaus-AM, was investigated in this study. Extracts and fractions of varying polarity from the wood, bark, and leaves were evaluated for antiplasmodial activity against the chloroquine-resistant K1 strain of Plasmodium falciparum. Results indicated that the most nonpolar extracts exhibited the greatest antimalarial potential, particularly the hexane extract of the bark (IC₅₀ = 5.73 μg/mL). Two tirucallane-type triterpenes, piscidinol A and niloticin, were isolated from the wood, along with the alkaloid 9-methoxycanthin-6-one, a compound characteristic of the genus Simaba. The presence of 9-methoxycanthin-6-one, considered a chemical marker of the Simaroubaceae family, adds to the chemophenetic understanding of the species. From the leaves, two flavonols (quercitrin and afzelin), a flavanol (epicatechin), two C-glycosylated flavones (vitexin and isovitexin), and methyl gallate were isolated. Afzelin demonstrated the most potent antimalarial activity (IC₅₀ = 8.88 μM), whereas epicatechin showed low activity (IC₅₀ = 125 μM). Methyl gallate (IC₅₀ = 15.1 μM) isolated from the plant, along with its synthetic analogues, were evaluated and it was observed that antimalarial activity decreased with increasing alkyl chain length. This study represents the first contribution to the understanding of the chemical composition of S. pubicarpa, providing a foundation for future investigations, particularly in the search for new natural-source antimalarial agents.