Microtubules are involved in many critical cellular processes including cell
division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of
tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly
efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the
tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent,
particularly in the development of transporter mediated drug resistance. While currently there
are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive
preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have
significantly less susceptibility to transporter medicated drug resistance. The presence of one or
more heterocyclic moieties is often critical for the antiproliferative activities for most of these
CBSIs. This article aims to review the structures and antiproliferative activities of most recently
developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that
are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the
colchicine binding site in tubulin.
Keywords: Heterocyclic tubulin inhibitors, colchicine binding site, CA-4 analogs, chalcone analogs, PTOX analogs.
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