title: Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4'-fluorophenyl)-imidazo[2,1-b][1,3,4]thiadiazole derivatives as potent anticancer agents.
abstract: Levamisole, the imidazo[2,1-b]thiazole derivative has been reported as a potential antitumor agent. In the present study, we synthesized, characterized and evaluated biological activity of its novel analogues with substitution in the aralkyl group and on imidazothiadiazole molecules with same chemical backbone but different side chains namely 2-aralkyl-6-(4'-fluorophenyl)-imidazo[2,1-b][1,3,4]thiadiazoles (SCR1), 2-aralkyl-5-bromo-6-(4'-fluorophenyl)-imidazo[2,1-b][1,3,4]-thiadiazoles (SCR2), 2-aralkyl-5-formyl-6-(4'-fluorophenyl)-imidazo[2,1-b][1,3,4]-thiadiazoles (SCR3) and 2-aralkyl-5-thiocyanato-6-(4'-fluorophenyl)-imidazo[2,1-b][1,3,4]-thiadiazoles (SCR4) on leukemia cells. The cytotoxic studies showed that 3a, 4a, and 4c exhibited strong cytotoxicity while others had moderate cytotoxicity. Among these we chose 4a (IC50, 8 μM) for understanding its mechanism of cytotoxicity. FACS analysis in conjunction with mitochondrial membrane potential and DNA fragmentation studies indicated that 4a induced apoptosis without cell cycle arrest suggesting that it could be used as a potential chemotherapeutic agent.
authors: Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India. subhasskarki@gmail.com
authors: Subhas S
authors: SS
authors: Karki
authors: Kuppusamy
authors: K
authors: Panjamurthy
authors: Sujeet
authors: S
authors: Kumar
authors: Mridula
authors: M
authors: Nambiar
authors: Sureshbabu A
authors: SA
authors: Ramareddy
authors: Kishore K
authors: KK
authors: Chiruvella
authors: Sathees C
authors: SC
authors: Raghavan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / 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; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C560936:2-benzyl-5-thiocyanato-6-(4'-fluorophenyl)imidazo(2,1-b)(1,3,4)thiadiazole; D000970:Antineoplastic Agents; D007093:Imidazoles; D013830:Thiadiazoles