Microwave assisted synthesis of some novel Flurbiprofen hydrazide hydrazones as anti-HCV NS5B and anticancer agents

The synthesis of a new series of flurbiprofen hydrazide-hydrazones using microwaveassisted reactions is described. Substituted aldehydes were condensed with flurbiprofenhydrazide by microwave irradiation to corresponding hydrazones. Synthesis ofN’-[(4-bromothiophen-2-yl)methylidene]-2-(2-fluorobiphenyl-4-yl) propanehydrazide (3o)employing microwave assisted process resulted in higher yields, in faster time and with lesschemical waste compared to traditional techniques. (2-fluorobiphenyl-4-yl)-N’-(phenylmethylidene)propanehydrazide (3p) and N’-[(2-chloro-6-fluorophenyl) methylidene]-2-(2-fluorobiphenyl-4-yl)propanehydrazide (3s) inhibited the growth of a leukemia cancercell line HL-60 (TB) by 66.37% and an ovarian cancer cell line OVCAR-4 by 77.34% (singledose, 10 μM), respectively at the National Cancer Institute (NCI), but had no significant effecton a panel of sixty human tumor cell lines. Flurbiprofen hydrazide-hydrazones wereweak inhibitors of hepatitis C virus NS5B polymerase activity with N’-[(5-ethylfuran-2-yl)methylidene]-2-(2-fluorobiphenyl-4-yl)propanehydrazide (3m) being the most active of thisseries. Binding mode investigations of compound 3m suggested that allosteric pocket (AP)-B may be the potential binding site for flurbiprofen hydrazones and these results will alsoassist in further derivatization of 3m using the green chemistry approach and improve thepotency of S-flurbiprofen hydrazide-hydrazones.