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

Abstract

a b s t r a c tHepatitis 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 hydrazideehydrazone scaffold as a promising hepatitis C virus (HCV) and hepatocelluler inhibitor. Herein we describe the design a number of 2 0 ,4 0 -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 0 ,4 0 -difluoro-4-hydroxy-N'-(2-pyridyl methylidene)biphenyl-3-carbohydrazide 3b and diflunisal (2.5e40 mM) 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 IC 50 values of 10, 10.34 16.21 4.74, 9.29 and 8.33 mM 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.

Hydrazide-hydrazones of 3-methoxybenzoic acid and 4-tert-butylbenzoic acid with promising antibacterial activity against Bacillus spp

“…Melting points were determined with Fisher-Johns blocks (Fisher Scientific, Schwerte, Germany) and are uncorrected. The 1 H NMR and 13 C NMR spectra were recorded on the Bruker Avance 300 apparatus (Bruker BioSpin GmbH, Munich, Germany) in DMSO-d 6 with TMS as the internal standard. The chemical shifts are expressed on the (ppm) scale with the use of TMS as the standard reference.…”

“…It is desirable to discover drugs with improved potency, wide activity spectrum and low toxicity 2 . In many reports, besides being useful building blocks for the synthesis of a variety of heterocyclic rings and in drug development 3,4 , hydrazide-hydrazones are considered to be good scaffolds for different pharmaceutical applications [5][6][7][8][9][10][11] and have a significant role to play as antimicrobial agents [12][13][14][15][16] . The biological activity associated with these compounds is attributed to the presence of the highly reactive azomethine group (-CO-NH-N¼CH-).…”

Synthesis and antibacterial activity of hnew hydrazide-hydrazones derived from Benzocaine

“…Benzocaine (ethyl 4-amino-benzoate) is a local anesthetic drug which contains esther funcionality. Hydrazidehydrazones have diverse biological activities [1][2][3][4][5][6][7][8][9][10][11][12].…”

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“…[11] A new N'-Acetyl propane sulfonic acid hydrazide [12] and other acid hydrazides [13] showed potential antibacterial activity. Şenkardeş et al [14] have designed a number of 2′,4′-difluoro-4-hydroxy-N'-(arylmethylidene)biphenyl-3-bohydrazide as anti-HCV and anticancer agents. Some hydrazides of (acridinyl-9-thio) acetic acid [15] proved to be moderately toxic and produced neurotropic, anti-inflammatory, analgesic, anti-microbial and fungi static effects.…”