A review of the recent developments of molecular hybrids targeting tubulin polymerization.

Microtubules are cylindrical protein polymers formed from αβ-tubulin heterodimers in  the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M  phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer  drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast  therapeutic advantages have been developed, but they often lead to multidrug resistance and ad?verse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin  polymerization. Molecular hybridization, based on the amalgamation of two or more pharmaco?phores of bioactive conjugates to engender a single molecular structure with enhanced pharmaco?kinetics and biological activity, compared to their parent molecules, has recently become a promis?ing approach in drug development. The practical application of combined active scaffolds targeting  tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different  designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and  detailed in the literature. This review describes various molecular hybrids with their reported struc?tural–activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin  polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be  modeled for improved tubulin polymerization inhibitory potency and hence, the development of  new therapeutic agents against cancer.