Monoterpene indole alkaloids with anticancer activity from Tabernaemontana species

Abstract

Indole alkaloids, predominantly found in plants, are a large group of natural product-derived compounds characterized by a remarkable chemical diversity associated with significant biological properties. Among these, terpenoid indole alkaloids are the largest group of secondary metabolites. Tabernaemontana species (Apocynaceae) are widely distributed in tropical and subtropical regions of the world and used in traditional medicine to treat a variety of illnesses, including tumours. These species biosynthesize large quantities of structurally complex monoterpene indole and bisindole alkaloids. Given the compelling biological properties of indole alkaloids, the phytochemical study of Tabernaemontana species has been widely addressed to identify potential anticancer compounds. Several indole alkaloids have shown antiproliferative effect due to different mechanisms, namely by inducing apoptosis or arresting cell cycle, in diverse cancer cell lines, including multidrug-resistant phenotypes. This review primarily aims to underscore the anticancer activity of indole and bisindole alkaloids isolated from several Tabernaemontana species. Moreover, our recent contributions to the field are also highlighted, focusing on the study of Tabernaemontana elegans. The anticancer evaluation, namely the reversion of P-glycoprotein-mediated multidrug resistance, of two sets of monoterpene indole alkaloid derivatives, obtained by modification of some functional groups of two major monoterpene indole alkaloids, is reviewed, as well as the results obtained for a derivative that targeted homologous recombination DNA repair defects.

Genome-based discovery of pachysiphine synthases inTabernaemontana elegans

“…The MIA dimers formed with pachysiphine and its distinct hydroxy, methoxy and N-methyl derivatives notably include conophylline, conophyllidine, conophyllinine, conofoline, conolodinines A-D or melodinine K have been broadly reported in numerous Tabernaemontana species (Achenbach et al, 1994;Zèches-Hanrot et al, 1995;Kam et al, 2003;Kojima and Umezawa, 2006;Sim et al, 2019). Because it is strongly mobilized to fulfill the biosynthesis of conophylline and related compounds, pachysiphine is thus accumulated in very low amounts in Tabernaemontana species, preventing any prospects for the supply of potent conophylline derivatives through semi-synthetic approaches (Gonçalves et al, 2024).…”