title: Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560 010, Karnataka, India.
authors.forename: Sujeet
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, Karnataka, India.
authors.forename: Vidya
authors.initials: V
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, Karnataka, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Hegde
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560 010, Karnataka, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Rana
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560 010, Karnataka, India.
authors.forename: Sharad S
authors.initials: SS
authors.lastname: Dhepe
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560 010, Karnataka, India.
authors.forename: Sureshbabu A
authors.initials: SA
authors.lastname: Ramareddy
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Leoni
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Locatelli
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Morigi
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Rambaldi
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, Karnataka, India.
authors.forename: Mrinal
authors.initials: M
authors.lastname: Srivastava
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, Karnataka, India.
authors.forename: Sathees C
authors.initials: SC
authors.lastname: Raghavan
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560 010, Karnataka, India. Electronic address: subhasskarki@gmail.com.
authors.forename: Subhas S
authors.initials: SS
authors.lastname: Karki
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D013830:Thiadiazoles; C586276:imidazo(2,1-b)(1,3,4)thiadiazole
keywords: Acute toxicity; Antiproliferative agents; Apoptosis; Cell-based screening assay; Hollow fiber assay; Imidazo[2,1-b][1,3,4]thiadiazoles