title: 2-(4-Chlorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazoles: synthesis, cytotoxic activity and mechanism of action.
abstract: The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle.
authors: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560010, India.
authors: Sujeet
authors: S
authors: Kumar
authors: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors: Mahesh
authors: M
authors: Hegde
authors: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors: Vidya
authors: V
authors: Gopalakrishnan
authors: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560010, India.
authors: Vinaya Kumar
authors: VK
authors: Renuka
authors: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560010, India.
authors: Sureshbabu A
authors: SA
authors: Ramareddy
authors: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors: Erik
authors: E
authors: De Clercq
authors: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors: Dominique
authors: D
authors: Schols
authors: Dept. of Physics, M. S. Ramaiah Institute of Technology, Bangalore 560054, India.
authors: Anil Kumar
authors: AK
authors: Gudibabande Narasimhamurthy
authors: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
authors: Sathees C
authors: SC
authors: Raghavan
authors: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560010, India. Electronic address: subhasskarki@gmail.com.
authors: Subhas S
authors: SS
authors: Karki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000596763:2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo(2,1-b)(1,3,4)thiadiazol-5-yl thiocyanate; C000596762:2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo(2,1-b)(1,3,4)thiadiazole-5-carbaldehyde; D000970:Antineoplastic Agents; D003603:Cytotoxins; D007093:Imidazoles; D013830:Thiadiazoles
keywords: Anti-cancer drugs; Apoptosis; Cancer therapeutics; Cell death; Cytotoxicity