A Comprehensive View on (-)-7-Oxo-ent-kaur-16-en-19-oic Acid, the Major Constituent of Xylopia sericea Leaves Extract: Complete NMR Assignments, X-Ray Crystallographic Structure, in Vitro Antimalarial Activity and Cytotoxicity

Abstract

Bioguided fractionation of Xylopia sericea antiplasmodial dichloromethane leaves extract led to the isolation of (-)-7-oxo-ent-kaur-16-en-19-oic acid (C₂₀ H₂₈ O₃ ) that was identified by a combination of 1D and 2D NMR experiments (COSY, HMBC, HSQC, HSQC-TOCSY, HSQC-NOESY and NOESY) and by X-ray crystallography. A feature to be pointed out is its (4R) configuration that was inferred from the NOE experiments (HSQC-NOESY and NOESY) and X-ray crystallography. In vitro evaluation of this rare diterpene acid against the chloroquine-resistant strain Plasmodium falciparum W2 by the PfLDH method showed it disclosed a low antiplasmodial activity and was not cytotoxic to HepG2 cells (CC₅₀ 862.6±6.7 μm) by the MTT assay. The unequivocal NMR signals assignments, the X-ray crystallographic structure, the assessment to the bioactivities and the occurrence this diterpene in X. sericea are reported here for the first time.

Keywords: Diterpene; LC-DAD-MS; X-ray crystallography; antiplasmodial activity; biological activity.