A Facile and Microwave-assisted Rapid Synthesis of 2-Arylamino-4-(3′-indolyl)- thiazoles as Apoptosis Inducing Cytotoxic Agents

Title:A Facile and Microwave-assisted Rapid Synthesis of 2-Arylamino-4-(3′-indolyl)- thiazoles as Apoptosis Inducing Cytotoxic Agents

Volume: 17 Issue: 3

Author(s): Mukund P. Tantak, Dipanwita Das Mukherjee, Anil Kumar, Gopal Chakrabarti and Dalip Kumar

Affiliation:

Keywords: Indoles, arylaminothiazoles, microwave irradiation, one-pot synthesis, cytotoxicity, apoptosis.

Abstract: Background and 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.

Method and 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).

Conclusion: 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.

Cite this article as:

Tantak P. Mukund, Mukherjee Das Dipanwita, Kumar Anil, Chakrabarti Gopal and Kumar Dalip, A Facile and Microwave-assisted Rapid Synthesis of 2-Arylamino-4-(3′-indolyl)- thiazoles as Apoptosis Inducing Cytotoxic Agents, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (3) . https://dx.doi.org/10.2174/1871520616666160622095406

DOI https://dx.doi.org/10.2174/1871520616666160622095406	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992