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Letters in Drug Design & Discovery
ISSN (Print): 1570-1808
ISSN (Online): 1875-628X
VOLUME: 11
ISSUE: 2
DOI: 10.2174/15701808113109990069      Price:  $58









Synthesis of 1-aroyl-3,5-dimethyl-1H-pyrazoles as Anti-HCV and Anticancer Agents

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Author(s): Sevil Aydın, Neerja Kaushik-Basu, Suna Özbaş-Turan, Jülide Akbuğa, Pınar Mega Tiber, Oya Orun, K. R. Gurukumar, Amartya Basu and Ş. Güniz Küçükgüzel
Pages 121-131 (11)
Abstract:
1-Aroyl-3,5-dimethyl-1H-pyrazole derivatives (7-12) were synthesized from some hydrazides (1-6) with acetylacetone (2,4-pentanedione) by microwave irradiation. Their structures were elucidated by FT-IR and 1H-NMR spectral data and elemental analysis. Compound activities were evaluated against HCV NS5B and in cell based HCV reporters. Compound 8 was the most promising of this series in inhibiting intracellular NS5B activity and HCV RNA replication in reporter cells. The selected compounds 9, 10 and 12 by National Institue of Health were screened for their anticancer activity against 60 human tumor cell lines. Compound 9 (3-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-2',4'- difluorobiphenyl-4-ol) possessed significant activity against human immortalized myelogenous leukemia (K-562) exhibiting cell growth promotion 30.05%, with inhibition of 69.95% at 10-5M concentration. Compounds 3 and 9 were evaluated for cell viability and growth inhibition by K-562 cells of MTT assay, at different doses (10-6- 10-2M). Further, compound 9 exhibited anticancer activity against K-562 cells with IC50 value of 4 µM . Apoptosis levels of compound 9 were determined for three different concentrations (10-6, 10-5 and 10-3M) at two time points (24 and 48 h). Compound 9 induced apoptosis of K-562 cells, thus suggesting that compound 9 might be a potential chemopreventive agent for chronic myelogenous leukemia.
Keywords:
Anticancer activity, Apoptosis, Diflunisal, Hepatitis C NS5B polymerase, Microwave, Pyrazole.
Affiliation:
Marmara University Faculty of Pharmacy Department of Pharmaceutical Chemistry Haydarpaşa 34668 İstanbul Turkey.