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.

Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity

“…As part of a recent summary account, further preclinical studies were described in a book chapter that led eventually to the evaluation of (+)-betulinic acid (1) in phase I/II clinical trials to treat dysplastic melanocytic nevi. These clinical trials were conducted at the College of Medicine, University of Illinois at Chicago, Chicago, IL, USA, with the drug administered topically as a 20 % ointment [20].…”

“…Cucurbitacins are highly oxygenated cucurbitane-type tetracyclic triterpenoids that were identified initially from the plant family Cucurbitaceae and have been divided into 12 major structural categories [63]. Members of this group of natural products have been reported for their promising anticancer and anti-inflammatory activities [64], of which (+)-cucurbitacins B (17) and D (18) and (−)-cucurbitacins E (19) and I (20) have been investigated extensively for their cytotoxicity toward several human cancer cell lines (▶ Fig. 4) [64,65].…”

“…Analysis of the structures of these potently cytotoxic triterpenoids, including (+)-cucurbitacins B (17) and D (18) and (−)-cucurbitacins E (19) and I (20), shows that they all contain a C-2 hydroxy group, a ketocarbonyl group at the C-3 and C-11 positions, a double bond at the C-1 and/or C-5 positions, 16α,20β-dihydroxy groups, a C-22 enone group, and a C-25 hydroxy or acetoxy group, indicating that these structural moieties could be important for a given cucurbitacin to mediate cancer cell-line cytotoxicity. This has been supported by a study examining the chemical structures of 24 cucurbitacins and determining their resultant cytotoxicity against KB human oral epidermoid carcinoma cells, which showed that the presence of an α,β-unsaturated ketone and a C-25 acetoxy group, along with a free 16α-hydroxy group, are the most relevant structural features required for such activity [65].…”

“…The antineoplastic potential of all (+)-cucurbitacins B (17) and D (18) and (−)-cucurbitacins E (19) and I (20) have been reviewed previously [64,65]. Briefly discussed below are an update of more recent studies on the anticancer potentials of the representative compound, (+)-cucurbitacin D (18).…”

Large-Scale Virtual Screening Against the MET Kinase Domain Identifies a New Putative Inhibitor Type

“…To include kinase-targeted compounds, as such a choice is already proven to be successful [41,42]; 3. To explore natural products, which are a promising source of anticancer drugs [43][44][45]; 4. To take into account the repositioning of approved compounds, as drug repurposing presents an increasing interest in cancer research, by removing many costs associated with several steps of drug development [46][47][48][49].…”