2. Academic Validation
  3. Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives

Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives

  • Bioorg Med Chem Lett. 2014 Oct 1;24(19):4682-4688. doi: 10.1016/j.bmcl.2014.08.032.
Sujeet Kumar 1,  Vidya Gopalakrishnan 2,  Mahesh Hegde 2,  Vivek Rana 1,  Sharad S Dhepe 1,  Sureshbabu A Ramareddy 1,  Alberto Leoni 3,  Alessandra Locatelli 3,  Rita Morigi 3,  Mirella Rambaldi 3,  Mrinal Srivastava 2,  Sathees C Raghavan 2,  Subhas S Karki 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560 010, Karnataka, India.
  • 2 Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, Karnataka, India.
  • 3 Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
  • 4 Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560 010, Karnataka, India. Electronic address: [email protected].
PMID: 25205189 DOI: 10.1016/j.bmcl.2014.08.032
Abstract

A series of 2,5,6-substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives have been prepared and were tested for antiproliferative activity on Cancer cells at the National Cancer Institute. Results showed that molecules with a benzyl group at position 2, exhibited an increase in activity for the introduction of a formyl group at the 5 position. The compound 2-benzyl-5-formyl-6-(4-bromophenyl)imidazo[2,1-b][1,3,4]thiadiazole 22 has been chosen for understanding the mechanism of action by various molecular and cellular biology studies. Results obtained from cell cycle evaluation analysis, analysis of mitochondrial membrane potential and Annexin V-FITC by flow cytometric analysis, ROS production and expression of apoptotic and DNA-repair proteins suggested that compound 22 induced cytotoxicity by activating extrinsic pathway of Apoptosis, however, without affecting cell cycle progression.

Keywords

Acute toxicity; Antiproliferative agents; Apoptosis; Cell-based screening assay; Hollow fiber assay; Imidazo[2,1-b][1,3,4]thiadiazoles.

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