Cytotoxic tazettine alkaloids of the plant family Amaryllidaceae

Abstract

From camptothecin to vinblastine, plant alkaloids continue to capture the imagination of scientists as a valuable source of anticancer drugs. Given that they are also amongst the most common secondary metabolites encountered in plants, the number of alkaloid entities subjected to cytotoxicity evaluations now runs into several thousands. Interest in the plant family Amaryllidaceae has been persistent owing to the potent cytotoxic activities of several of its isoquinoline alkaloid principles. This survey is an indepth account of such properties discernible for tazettine alkaloids belonging to the minor alkaloid groups of the Amaryllidaceae. Eleven of such compounds have up to now been screened against around 50 cancer cell lines which may be classified into nearly 20 different types of cancers. Although the activities in most instances were moderate to mild, notable responses were observed against some leukemia, adenocarcinoma, lymphoma and glioblastoma cell lines. In fact, pretazettine (ED50 0.3 μg/mL) was amongst the most potent of all Amaryllidaceae alkaloids screened against the human Molt4 T-lymphoma cell line. To most accounts, the parent compounds (such as tazettine and pretazettine) with their distinct ring systems and substitution patterns exhibit the best activities, offering little space for structural adjustments via semi-synthetic operations. Several avenues have been probed in attempts to elucidate the mechanisms by which tazettine alkaloids manifest their cytotoxic effects including, inhibition of protein synthesis, apoptosis and efflux pump interactions, the first of which to date offers the most profound insights.