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Microtubules are a protein which is made of α- and β-heterodimer. It is one of the main components of the cell which play a vital role in cell division especially in G2/M-phase. It exists in equilibrium dynamic of polymerization and depolymerization of α- and β-heterodimer. It is one of the best targets for developing anti-cancer drugs. Various natural occurring molecules are well known for their anti-tubulin effect such as vinca, paclitaxel, combretastatin, colchicine etc. These microtubule-targeted drugs are acted through two processes (i) inhibiting depolymerization of tubulin (tubulin stabilizing agents) and (ii) inhibiting polymerization of tubulin (tubulin destabilizing agents). Now days, various binding domains have been explore through which these molecules are binding to tubulin but the three major binding domain of tubulin are taxol, vinca and colchicine binding domain. The present article mainly focus on the classification of various naturally occurring compounds on the basis of their inhibition processes (depolymerization and polymerization) and the site of interaction (targets taxol, vinca and colchicine binding domain) which has been hitherto reported. By placing all the naturally occurring taxol, vinca and colchicine binding site analogues at one place makes a better understanding of the tubulin interactions with known natural tubulin binders that would helps in the discovery of new and potent natural, semi-synthetic and synthetic analogues for treating cancer., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

A series of 1,3,4-oxadiazole (11a-n) and 1,2,4-Triazole (12a, c, e, g, h, j-n) based topsentin analogues were synthesized and evaluated for their anti-proliferative activities. Compounds 11d 12e, and 12h demonstrated excellent anti-proliferative activity against MCF-7 Cancer cell line with IC 50 3.06 µM, 3.30 µM and 2.42 µM respectively. 11d caused cell arrest at G0/G1 phase and disrupted mitochondrial membrane potential with reduced cell migration of MCF-7 cells in dose dependent manner. 11d disrupt tubulin dynamics by inhibiting tubulin polymerization with IC 50 3.89 μM. • New 1,3,4-oxadiazole (11a-n) and 1,2,4-Triazole (12a, c, e, g, h, j-n) based topsentin analogues were synthesized. • Compound 11d exhibited anti-proliferative activity against MCF-7 cancer cell line with IC 50 3.06. • 11d caused cell arrest at G0/G1 phase and disrupted mitochondrial membrane potential with reduced cell migration of MCF-7 cells in dose dependent manner. • 11d disrupted tubulin dynamics by inhibiting tubulin polymerization with IC 50 3.89 μM. A set of two series of 1,3,4-oxadiazole (11a-n) and 1,2,4-Triazole (12a, c, e, g, h, j-n) based topsentin analogues were prepared by replacing imizadole moiety of topsentin through a multistep synthesis starting from indole. All the compounds synthesized were submitted for single dose (10 µM) screening against a NCI panel of 60-human cancer cell lines. Among all cancer cell lines, colon (HCC-2998) and Breast (MCF-7, T-47D) cancer cell lines were found to be more susceptible for this class of compounds. Among the compounds tested, compounds 11a, 11d, 11f, 12e and 12h, were exhibited good anti-proliferative activity against various cancer cell lines. Compounds 11d, 12e and 12h demonstrated better activity with IC 50 2.42 µM, 3.06 µM, and 3.30 µM respectively against MCF-7 human cancer cell line than that of the standard drug doxorubicin IC 50 6.31 µM. Furthermore, 11d induced cell cycle arrest at G0/G1 phase and also disrupted mitochondrial membrane potential with reducing cell migration potential of MCF-7 cells in dose dependent manner. In vitro microtubule polymerization assays found that compound 11d disrupt tubulin dynamics by inhibiting tubulin polymerization with IC 50 3.89 μM compared with standard nocodazole (IC 50 2.49 μM). In silico docking studies represented that 11d was binding at colchicine binding site of β-tubulin. Compound 11d emerged as lead molecule from the library of compounds tested and this may serve as a template for further drug discovery. [ABSTRACT FROM AUTHOR]