Recent Trends in Tubulin-Binding Combretastatin A-4 Analogs for Anticancer Drug Development

: Although significant progress over several decades has been evidenced in cancer therapy, there still remains a need for the development of novel and effective therapeutic strategies to treat several relapsed and intractable cancers. In this regard, tubulin protein has become one of the efficient and major targets for anticancer drug discovery. Considering the antimitotic ability, several tubulin inhibitors have been developed to act against various cancers. Among various tubulin inhibitors available, combretastatin-A4 (CA-4), a naturally occurring lead molecule, offers exceptional cytotoxicity (including the drug-resistant cell lines) and antivascular effects. Although CA-4 offers exceptional therapeutic efficacy, several new advancements have been proposed, such as the structural modification via A and B rings, as well as cis-olefinic bridging, which provide highly efficient analogs with improved tubulin-binding efficiency to meet the anticancer drug development requirements. This review systematically emphasizes the recent trends and latest developments in the anticancer drug design & discovery, using CA-4 analogs as the tubulin inhibiting agents, highlighting their structure-activity relationships (SAR) and resultant pharmacological efficacies.