Synthesis and Biological Evaluation of Novel Thiazol-2yl-amine Derivatives as Potential Anticancer Agents

Author(s): Chaithanya Somu, Mahesh Hegde, Kothanahally S. Sharath Kumar, Ananda Hanumappa, Mrinal Srivastava, Kachigere B. Harsha, Chakrabhavi D. Mohan, Kavya Ananthaswamy, Basappa, Sathees C. Raghavan, Kanchugarakoppal S. Rangappa*

Journal Name: Letters in Organic Chemistry

Volume 15 , Issue 4 , 2018

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Graphical Abstract:


Background: Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that can occur in any age group but often seen in adults and contributing for about 20% of adult leukemias and it may contribute up to 15% of all types of leukemias threatening the globe. Therefore, treatment of CML remains as a major challenge in cancer therapeutics.

Methods: We synthesized a library of novel 2-amino-4-(4-substituted phenyl) thiazole derivatives and evaluated their anti-leukemic activity by trypan blue and MTT assay. 4-(4'-phenoxybiphenyl-4-yl) thiazol- 2-amine (compound 3m) was identified as a lead anticancer agent and further, the effect of 3m on CML cells (K562) was investigated by flow cytometry, annexin V-FITC-propidium iodide staining, measuring the mitochondrial membrane potential (JC-1 staining) and DNA fragmentation assay.

Results: MTT and trypan blue dye exclusion assay results presented 3m as the lead anticancer agent. Flow cytometric analysis revealed the accumulation of K562 cells in subG1phase in a time- and dosedependent manner. Annexin-V-FITC-PI staining demonstrated the increase in percentage of apoptotic cells on treatment with 3m. Furthermore, 3m also induced DNA fragmentation and disrupted mitochondrial membrane potential in K562 cells in dose-dependent manner. In addition, apoptosis inducing effect of 3m was reconfirmed by live-dead assay and confocal microscopic studies.

Conclusion: The present study suggests that compound 3m has the potential to be a promising candidate for the treatment of CML.

Keywords: Anticancer agent, chemotherapeutics, hantsch reaction, K562, suzuki coupling, thiazole.

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Article Details

Year: 2018
Page: [270 - 281]
Pages: 12
DOI: 10.2174/1570178614666170907122026
Price: $65

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