Phytochemical investigation of naphthylisoquinoline alkaloids from ancistrocladus sp. (banalia) related to ancistrocladus likoko with potential antiplasmodial activity

Abstract

Malaria is a major global health concern, particularly in the sub-Saharan regions of Africa, where it remains a leading cause of morbidity and mortality. The growing resistance of malaria parasites to commonly used antimalarial drugs further exacerbates the situation, highlighting the urgent need for the development of novel and more effective antimalarial medicines. Plants used in traditional medicine constitute valuable sources of potential antimalarial lead compounds. Among them, are Ancistrocladus species, traditionally used by indigenous populations across the globe for the treatment of various diseases, including malaria. Ancistrocladus plants have drawn considerable scientific interest over recent decades due to their unique content of naphthylisoquinoline (NIQ) alkaloids, which constitute an emerging class of secondary metabolites with more than 280 representatives. NIQs are remarkable for their structural diversity, unprecedented biosynthetic origin, and promising pharmacological properties, including excellent in vitro and in vivo antiplasmodial activities. The present study provides the first in-depth phytochemical investigation of root bark extracts from an Ancistrocladus species collected in Banalia, eastern part of the Congo basin, and, which shares morphological features with the botanically acknowledged Ancistrocladus likoko, also found in the evergreen Congo rainforest. The phytochemical study involved an ultrasound-assisted delipidation and extraction of NIQs, followed by the enrichment of the crude NIQ-containing extract through liquid–liquid partitioning. Subsequently, isolation of NIQs was achieved through column chromatography and/or preparative HPLC. Structure elucidation of isolated compounds, including the determination of the relative and absolute configuration at elements of chirality, was carried out using a combination of spectrometric (HR-ESI-MS) and spectroscopic (1D- and 2D-NMR, UV, and ECD) techniques, which resulted in the identification of two known 5,8’-coupled monomeric NIQs, namely ancistrolikokine C (44) and korupensamine A (46). Chemotaxonomically, both compounds were 3R-configured and oxygenated in C-6, which are structural features that are characteristic for hybrid-type NIQs specific to Ancistrocladus plants from the Congo basin. As previously reported in the literature, compounds 44 and 46 demonstrated good and excellent antiplasmodial activity, respectively, identifying them as promising scaffolds for antimalarial drug development.