Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy.

The phenanthroindolizidine and phenanthroquinolizidine alkaloids, typified by tylophorine and cryptopleurine, are a family of plant-derived small molecules with significant therapeutic potential. The plant extracts have been used in herbal medicine and the isolated compounds have displayed a range of promising therapeutic activity such as anti-ameobicidal, anti-viral, anti-inflammatory and anti-cancer activity. Despite their therapeutic protential, no compounds in this class have fully passed clinical trials. Drawbacks include low in vivo anti-cancer activity, central nervous system toxicity and low natural availability. A number of biological effects of these compounds, such as protein and nucleic acid synthesis suppression, have been identified, but the specific biomolecular targets have not yet been identified. Significant effort has been expended in the synthesis and structure-activity-relationship (SAR) studies of these compounds with the hope that a new drug will emerge. This review will highlight important contributions to the isolation, synthesis, SAR and mechanism of action of the phenanthroindolizidine and pheanthroquinolizidine alkaloids.