2-Pyridineformamide N(4)-ring incorporated thiosemicarbazones inhibit MCF-7 cells by inhibiting JNK pathway. Issue 13 (1st July 2019)

• Record Type: Journal Article
• Authors: Shakya, Bhushan; Shahi, Nerina; Ahmad, Faiz; Yadav, Paras Nath; Pokharel, Yub Raj
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 13(2019)
• Page Start: 1677
• Page End: 1681
• Publication Date: 2019-07-01
• Subjects: A431 -- A375 -- Cell viability -- HeLa -- MCF-7 -- 2-Pyridineformamide thiosemicarbazone; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.04.031
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In an effort to develop a more potent anticancer therapeutic agent, a series of 2-pyridineformamide thiosemicarbazones (R = H, 4-CH3, 5-F, 6-CH3 and ) have been synthesized and evaluated for their anti-cancer activities against the cancer cells MCF-7 (breast cancer cell line), A-431 and A375 (epidermoid carcinoma cell line), and HeLa (cervical cancer cell line) using MTT assay. All these 2-pyridineformamide thiosemicarbazones exhibited anti-proliferative activities towards these cell lines.5FAmPyrr possess most profound effects against MCF-7 cells with IC50 of 0.9 µM. In flow cytometry using Propidium Iodide, 5FAmPyrr was found to induce cell death significantly in a dose dependent manner (100 nM–3 µM) and inhibited colony formation of MCF-7 cells. This compound induced pro-apoptotic protein Bax and inhibited anti apoptotic protein Bcl-2 as well as both c-Jun and Jun N -terminal kinase (abbreviated as JNK) in concentration dependent manner. Further pro-caspase 3 and PARP were inhibited by5FAmPyrr at concentration of 3 µM. The results suggest that5FAmPyrr exhibit anticancer potency and induced cell death by inhibiting MAPK signaling and inducing intrinsic apoptotic pathway. All these indicate that 2-pyridineformamide thiosemicarbazones could be developed as future therapeutics agents to treat cancer.