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

Abstract

ABSTRACT: The synthesis of a new series of flurbiprofen hydrazide-hydrazones using microwave
assisted reactions is described. Substituted aldehydes were condensed with flurbiprofen
hydrazide by microwave irradiation to corresponding hydrazones. Synthesis of
N’-[(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 less
chemical 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 cancer
cell line HL-60 (TB) by 66.37% and an ovarian cancer cell line OVCAR-4 by 77.34% (single
dose, 10 μM), respectively at the National Cancer Institute (NCI), but had no significant effect
on a panel of sixty human tumor cell lines. Flurbiprofen hydrazide-hydrazones were
weak 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 this
series. 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 also
assist in further derivatization of 3m using the green chemistry approach and improve the
potency of S-flurbiprofen hydrazide-hydrazones.
KEY WORDS: anticancer activity, E-Z isomerism, flurbiprofen, hepatitis C NS5B polymerase,
hydrazide-hydrazone, microwave.

Keywords

• anticancer activity, E-Z isomerism, flurbiprofen, hepatitis C NS5B polymerase, hydrazide-hydrazone, microwave.

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

Abstract

References

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