Combretastatin A-4 based compounds as potential anticancer agents: A review
Mai H Omar1, Soha H Emam1, Demiana S Mikhail1
1Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Abstract:
The current review discusses the importance of combretastatin A-4 (CA-4) as a lead compound of microtubule targeting agents. CA-4 holds a unique place among naturally occurring compounds having cytotoxic activity. In this review an overall picture of design strategies, structure-activity relationship, synthesis, cytotoxic activity, and binding interactions of promising CA-4 analogues, are discussed and arranged chronologically from 2016 to early 2023. Also, this review emphasizes their biological activity as anticancer agents, within an overview of clinical application limitation and suggested strategies to overcome. Dual targeting tubulin inhibitors showed highpotentialto surpass medication resistance and provide synergistic efficacy. Linking platinum (IV), amino acids, and HDAC targeting moieties to active tubulin inhibitorsproduced potent active compounds. Analogues of CA-4 bridged with azetidin-2-one, pyrazole, sulfide, or carrying selenium atom exhibited cytotoxic action against a variety of malignant cell lines through different pathways.
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