Synthesis of novel diflunisal hydrazide hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors

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Date

2016-01-27

Author

ŞENKARDEŞ, SEVİL
Kaushik-Basu, Neerja
Durmaz, Irem
Manvar, Dinesh
Basu, Amartya
Atalay, Rengül
KÜÇÜKGÜZEL, ŞÜKRİYE GÜNİZ

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Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. We have previously identified the hydrazide hydrazone scaffold as a promising hepatitis C virus (HCV) and hepatocelluler inhibitor. Herein we describe the design a number of 2',4'-difluoro-4-hydroxy-N'-(arylmethylidene) biphenyl-3-carbohydrazide (3a-t) as anti-HCV and anticancer agents. Results from evaluation of anti-HCV activity indicated that most of the synthesized hydrazone derivatives inhibited viral replication in the Huh7/Rep-Feo1b and Huh 7.5-FGR-JCI-Rluc2A reporter systems. Antiproliferative activities of increasing concentrations of 2',4'-difluoro-4-hydroxy-N'-(2-pyridyl methylidene)biphenyl-3-carbohydrazide 3b and diflunisal (2.5-40 mu M) were assessed in liver cancer cell lines (Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475) with sulforhodamine B assay for 72 h. Compound 3b with 2-pyridinyl group in the hydrazone part exhibited promising cytotoxic activity against all cell lines with IC50 values of 10, 1034 16.21 4.74, 9.29 and 8.33 mu M for Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G0 phase as an indicator of apoptotic cell death induction. (C) 2015 Elsevier Masson SAS. All rights reserved.

Subject Keywords

Diflunisal, Hydrazideehydrazone, Hepatitis C, Hepatocellular carcinom, Antiviral

URI

https://hdl.handle.net/11511/32241

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

DOI

https://doi.org/10.1016/j.ejmech.2015.10.041

Collections

Graduate School of Informatics, Article

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Citation Formats

S. ŞENKARDEŞ et al., “Synthesis of novel diflunisal hydrazide hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors,” EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, pp. 301–308, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/32241.