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

Ahmed Kamal, P. S. Srikanth, M. V.P.S. Vishnuvardhan, G. Bharath Kumar, Korrapati Suresh Babu, S. M.Ali Hussaini, Jeevak Sopanrao Kapure, Abdullah Alarifi

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)126-136
Number of pages11
JournalBioorganic Chemistry
Volume65
DOIs
StatePublished - 1 Apr 2016
Externally publishedYes

Keywords

  • 1,3,4-Oxadiazole
  • Apoptotic cell death
  • Colchicine binding
  • Molecular modeling
  • Tubulin polymerization

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