title: A Facile and Microwave-assisted Rapid Synthesis of 2-Arylamino-4-(3'-indolyl)- thiazoles as Apoptosis Inducing Cytotoxic Agents.
abstract: OBJECTIVE
  The clinical success of the chemotherapeutic drugs is restricted by the nonspecific toxicity-related adverse side effects. The diverse implication of indoles and thiazoles in medicinal chemistry prompted us to develop a new series of novel 2-aryl-amino-4-(3'-indolyl)thiazoles as more effective and less toxic anti-cancer compounds.
  
  
  RESULTS
  One-pot microwave-assisted rapid and high yielding synthesis of 2-arylamino-4-(3'- indolyl)thiazoles involved the reaction of easily available α-tosyloxy-ketones with N-arylthioureas in polyethylene glycol-400 (PEG-400). In vitro cytotoxicity study of 2-arylamino-4-(3'-indolyl)thiazoles against a panel of human cancer cell lines by MTT assay revealed IC50 values in the low micromolar range. Of the fifteen synthesized arylaminothiazoles, compounds 17b, 17d, 17g and 17il showed significant anti-proliferative activity against the selected cancer cell lines with IC50 < 10 μM. The compound 17b was identified as the most potent ligand of the series, which exhibited good cytotoxic activity against MCF-7 breast cancer cells with an IC50 value of 1.86 μM but minimal toxicity on normal human cells. Investigation of the underlying mechanism by flow cytometry indicated that 17b induced ROS-mediated apoptosis in MCF-7 cells in a dose-dependent manner as supported by upregulation of Bax and caspase-3 and down-regulation of Bcl-2 (by Western blot).
  
  
  CONCLUSIONS
  Developed an efficient and eco-friendly synthesis for 2-arylamino-4-(3'-indolyl)thiazoles, and their in vitro cytotoxicity studies demonstrate that compound 17b exhibits significant anti-proliferative activity against MCF-7 (breast cancer) cells by activating ROS-mediated apoptosis through the mitochondrial apoptosis pathway.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
authors.forename: Mukund P
authors.initials: MP
authors.lastname: Tantak
authors.affiliation: Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, India.
authors.forename: Dipanwita Das
authors.initials: DD
authors.lastname: Mukherjee
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology and Dr. B.C. Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Chakrabarti
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
authors.forename: Dalip
authors.initials: D
authors.lastname: Kumar
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; D008872:Microwaves; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D013844:Thiazoles
keywords: Indoles; apoptosis; arylaminothiazoles; cytotoxicity; microwave irradiation; one-pot synthesis