Combretastatin A-4 (CA-4) is one of the most potent antimitotic agents, showing strong cytotoxicity against a variety of cancer cells. Besides, it is an angiogenesis inhibitor and causes tumor blood vessels shut down. Currently, there are several CA-4 derivatives in clinical trials. Florine-containing compounds have been widely used in medicinal chemistry because the incorporation of fluorine often furnishes molecules with unique properties that cannot be attained using any other element. So a small library of fluorinated combretastatin analogs was designed, synthesized and evaluated.<br/>Docking studies were carried out to investigate the binding mode and affinity between Combretastatin analogs and tubulin (PDB code: 4O2B). The influence of the fluorine atom on Combretastatin scaffold was also evaluated, in silico. Fluorinated analogs were screened and ranked by binding affinity by Autodock and Moe. During screening, several analogs with better energy scores than CA-4 were found. Those fluorine-containing combretastatin analogs with good docking energy score were synthesized and evaluated.

Computational structural-based design and structure and activity study of fluorinated combretastatin analogues

253rd National Meeting (2017)

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