Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents

Ahmed Kamal, T. Srinivasa Reddy, M. V.P.S. Vishnuvardhan, Vijaykumar D. Nimbarte, A. V. Subba Rao, Vunnam Srinivasulu, Nagula Shankaraiah

Research output: Contribution to journalArticlepeer-review


A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 μM) which showed GI50 values in the range of 0.79-28.2 μM. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis by DNA fragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds.

Original languageEnglish (US)
Pages (from-to)4608-4623
Number of pages16
JournalBioorganic and Medicinal Chemistry
Issue number15
StatePublished - Jul 23 2015
Externally publishedYes


  • 1,2,4-Oxadiazole
  • Apoptosis
  • Benzimidazole
  • Cytotoxicity
  • Molecular docking
  • Tubulin polymerization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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