Editor-in-Chief İlkay Küçükgüzel Associate Editor Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Marmara Pharmaceutical Journal 2013 , Vol 17 , Issue 1
Microwave assisted synthesis of some novel Flurbiprofen hydrazidehydrazones as anti-HCV NS5B and anticancer agents
Sevil Aydın1, Neerja Kaushik-Basu2, Payal Arora2, Amartya Basu2, Daniel Brian Nichols2, Tanaji T Talele3, Mehmet Akkurt4, İsmail Çelik5, Orhan Büyükgüngör6, Ş. Güniz Küçükgüzel1
1Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, İstanbul, Turkey
2UMDNJ-New Jersey Medical School, Department of Biochemistry and Molecular Biology, Newark, USA
3St. John's University, Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Jamaica
4Erciyes University, Department of Physics Faculty of Arts and Sciences, Kayseri, Turkey
5Cumhuriyet University, Department of Physics Faculty of Arts and Sciences, Sivas, Turkey
6Ondokuz Mayıs University, Department of Physics Faculty of Arts and Sciences, Samsun, Turkey
DOI : 10.12991/201317389 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. Keywords : anticancer activity, E-Z isomerism, flurbiprofen, hepatitis C NS5B polymerase, hydrazide-hydrazone, microwave
Marmara University