Synthesis Of Anti-tumour Agent Combretastatin-4 And Derivatives

Cancerogenic diseases cause a significant number of deaths and are very difficult in treatment. Most of the anticancer drugs exhibit high toxicity, undesired side effects and cause hypersensitive reaction. A serious drawback of the drugs, which are in use, is the frequent occurrence of multidrug resistance. The search for new drugs and effort toward their modification continually attracts the interest of scientists. Chemical modification of the molecule of a known drug may lead to compounds exhibiting new properties, which is an advantageous from to develop new anti-cancer drug.The Combretaceae family of shrubs and trees is widely employed in traditional medicine in Africa and India. Researcher began a study of cancer cell growth inhibitors present in the African willow tree Combretum caffrum that resulted in isolation and structural determination of a series of active compound. The most potent of these is combretastatin A-4(CA-4). CA-4 has been studied intensively because of its potent anti-cancer activity. CA-4 not only is a new cytotoxic agent (target in tubulin protein), but also is a tumor angiogenesis inhibitor and it is relatively inactive in normal tissues. Tubulin protein is a major target for anticancer drug discovery. Consequently, a number of CA-4 analogues has been synthesized and evaluated. As a result, antimitotic agents constitute an important class of the current anticancer drug.In this paper, a new process for preparing CA-4 was provided. CA-4 was synthesized from inexpensive isovanillin by six-step reactions in an overall yield of 25.8%. In the same time, a new series of CA-4 analogues was synthesized, including modification of the B-ring of CA-4 and replace the alkene with β-lactam. The chemical structure of the product was determined by IR and 1HNMR. In the near future, our term will synthesize more derivative of CA-4 and evaluate the activity of new analogues in Vitro and in Vivo. According to SAR (Structure-Activity Relationship), new analogues of CA-4 will be designed and synthesized.