A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii

Abstract

Phytochemical investigations of ethanol root bark and stem bark extracts of <i>Cleistochlamys kirkii</i> (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, <b>1</b>) alongside 12 known compounds (<b>2</b>-<b>13</b>). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds <b>5</b> and <b>10</b> were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of <i>C. kirkii</i> root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite <i>Plasmodium falciparum</i> at 0.01 μg/mL. The isolated metabolites dichamanetin, (<i>E</i>)-acetylmelodorinol, and cleistenolide showed IC₅₀ = 9.3, 7.6 and 15.2 μM, respectively, against <i>P. falciparum</i> 3D7. Both the crude extract and the isolated compounds exhibited cytotoxicity against the triple-negative, aggressive breast cancer cell line, MDA-MB-231, with IC₅₀ = 42.0 μg/mL (crude extract) and 9.6-30.7 μM (isolated compounds). Our findings demonstrate the potential applicability of <i>C. kirkii</i> as a source of antimalarial and anticancer agents.