Combretastatins are group of stilbenes (C6-C2-C6 heartwood constituents seen in Combretum, Santalum, Pinus etc) exhibiting excellent antitubulin properties and act as anticancer agents directed against tubulin.
They bind and destabilize the polymeric structure of microtubules, thus causing microtubule disassembly( thus inhibit the polymerization of tubulin) and stops cell division in the middle stage of mitosis, and is a cell cycle-specific drug.
These compounds are found in the bark of of a south African tree Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow.
The bark is found to contain related compounds such as dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D).
Some of the compounds in this series have been shown to be among the most potent antitubulin agents known.
As they are structuraly simple (2 benzene rings attached by 2carbons) many analogs have also been synthesized. Combretastatin A4 phosphateis the most frequently tested compounds in preclinical and clinical trials.
It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. Other beneficial properties are antioxidant, anti-inflammatory and antimicrobial effects.
Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects.
References
G. Ş. Karatoprak and co-workers (2020) Combretastatins:
An Overview of Structure, Probable Mechanisms of Action and Potential Applications, Molecules Molecules 2020, 25, 2560; doi:10.3390/molecules25112560
Mammen Daniel
