Combretastatin A-4 analogs: Past, present, and future directions

Microtubules are protein biopolymers created by polymerizing heterodimers of α and β-tubulins. Microtubule disruption induces G2/M cell cycle arrest and abnormal mitotic spindle formation. Microtubules are vital for cell division; without them, cell division cannot occur. Chemotherapeutic interference with tubulin/microtubule polymerization dynamics . Their significance in cell division makes microtubules an appealing target for anticancer drug discovery. Several naturally occurring compounds, such as vinblastine, paclitaxel, combretastatin, and colchicine exert their activity by changing tubulin dynamics, such as polymerization and depolymerization. Tubulin, an essential tumor therapy target, is one of the hotspots in the area of antineoplastic drugs, and it is of a significance importance to design novel inhibitors for this target. Both natural and synthetic scaffolds are the main tubulin inhibitors sources. In this article, the main structural features and motifs tubulin polymerization inhibitors are reviewed. Thus, it provides a theoretical basis for target optimization of new inhibitors of tubulin polymerization.