The Search for Anticancer Agents from Tropical Plants

Abstract

Many of the clinically used anticancer agents in Western medicine are derived from secondary metabolites found in terrestrial microbes, marine organisms, and higher plants, with additional compounds of this type being currently in clinical trials. If plants are taken specifically, it is generally agreed that the prospects of encountering enhanced small organic-molecule chemical diversity are better if tropical rather than temperate species are investigated in drug discovery efforts. Plant collection in tropical source countries requires considerable preparation and organization to conduct in a responsible manner that abides by the provisions of the 1992 Rio Convention of Biological Diversity and the 2010 Nagoya Protocol on Access to Genetic Resources. Correct taxonomic identifications and enhanced procedures for processing and documenting plant samples when collected in often difficult terrain are required. Phytochemical aspects of the work involve solvent fractionation, known compound dereplication, preliminary in vitro testing, and prioritization, leading to "activity-guided fractionation", compound structure determination, and analog development. Further evaluation of lead compounds requires solubility, formulation, preliminary pharmacokinetics, and in vivo testing in suitable models. Covering the work of the authors carried out in two sequential multidisciplinary, multi-institutional research projects, examples of very promising compounds discovered from plants acquired from Africa, Southeast Asia, the Americas, and the Caribbean region, and with potential anticancer activity will be mentioned. These include plant secondary metabolites of the diphyllin lignan, cyclopenta[b]benzofuran, triterpenoid, and tropane alkaloid types.