Combretastatin linked 1,3,4-oxadiazole conjugates as a Potent Tubulin Polymerization inhibitors

• A new series of combretastatin linked 1,3,4-oxadiazoles were designed and synthesized.
• These conjugates are screened for their cytotoxic activity.
• Conjugate 5m displayed potent antiproliferative activity against DU-145 cell line with IC50 value 0.118 μM.
• These conjugates induced cell cycle arrest at G2/M phase in cell cycle analysis.
• These conjugates effectively inhibit tubulin polymerization.

A new class of combretastatin linked 1,3,4-oxadiazoles were designed, synthesized and screened for their cytotoxic activity against five human cancer cell lines such as HeLa, DU-145, A549, MDA-MB-231 and B16. These compounds showed significant cytotoxicity with IC50 values in the range 0.118–54.32 μM. Conjugate 5m displayed potent antiproliferative activity against DU-145 cell line. Flow cytometric analysis revealed that these compounds arrested the cell cycle in G2/M phase. Moreover, the tubulin polymerization assay and immunofluorescence analysis indicate that 5m exhibits potent inhibitory effect on the tubulin assembly. Further, DNA fragmentation and Hoecst staining assays confirm that 5m induces apoptosis. Molecular docking studies and competitive binding assay indicated that 5m effectively bind at the colchicine binding site of the tubulin.

A new class of combretastatin linked to oxadiazole have synthesized and evaluated for their anticancer activity. The tubulin polymerization assay and immunofluorescence analysis indicate that exhibits potent inhibitory effect on the tubulin assembly also these are effectively bind at the colchicine binding site of the tubulin.Figure optionsDownload as PowerPoint slide