Author/Authors :
Aydın, Sevil Marmara University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry, Turkey , Kaushik-Basu, Neerja University of Medicine and Dentistry of New Jersey (UMDNJ) - Medical School - Department of Biochemistry and Molecular Biology, USA , Arora, Payal University of Medicine and Dentistry of New Jersey (UMDNJ) - Medical School - Department of Biochemistry and Molecular Biology, USA , Basu, Amartya University of Medicine and Dentistry of New Jersey (UMDNJ) - Medical School - Department of Biochemistry and Molecular Biology, USA , Nichols, Daniel Brian University of Medicine and Dentistry of New Jersey (UMDNJ) - Medical School - Department of Biochemistry and Molecular Biology, USA , Talele, Tanaji T St. John’s University - College of Pharmacy and Allied Health Professions - Department of Pharmaceutical Sciences, USA , Akkurt, Mehmet Erciyes University - Faculty of Sciences - Department of Arts and Physics, TURKEY , Çelik, İsmail Cumhuriyet University - Faculty of Arts and Sciences - Department of Physics, Turkey , Büyükgüngör, Orhan Ondokuz Mayis University - Faculty of Arts and Sciences - Department of Physics, TURKEY , Küçükgüzel, Güniz Marmara University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry, Turkey
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 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 also assist in further derivatization of 3m using the green chemistry approach and improve the potency of S-flurbiprofen hydrazide-hydrazones.
NaturalLanguageKeyword :
anticancer activity , E , Z isomerism , flurbiprofen , hepatitis C NS5B polymerase , hydrazide , hydrazone , microwave
