Synthesis and biological evaluation of novel 4,5-dihydropyrazole derivatives as potent anticancer and antimicrobial agen
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Med Chem Res (2013) 22:2061–2078 DOI 10.1007/s00044-012-0191-y
ORIGINAL RESEARCH
Synthesis and biological evaluation of novel 4,5-dihydropyrazole derivatives as potent anticancer and antimicrobial agents Y. Rajendra Prasad • G. V. Suresh Kumar S. M. Chandrashekar
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Received: 26 April 2012 / Accepted: 6 August 2012 / Published online: 2 September 2012 Ó Springer Science+Business Media, LLC 2012
Abstract A focused library of 4,5-dihydropyrazole dervivatives (4, 5, 6, 7a–h, 8, 9a–g, and 10a–g) were synthesized from novel 5-(2,6-difluorophenyl)-3-phenyl-4,5-dihydropyrazole-1-carbothioamide 4. The synthesized compounds were characterized using elemental analysis and spectral data (IR, mass spectra, 1H and 13C NMR) and evaluated for antimicrobial activity by broth dilution method and in vitro anticancer activity. Among the synthesized compounds 7a, 9c, 9g, and 10d exhibit broad spectrum antimicrobial activity against tested microbial strains. The in vitro cancer results ascertain 7a, 9c, and 10d are most potent molecules in comparison to reference standard cisplatin. Keywords 4,5-Dihydropyrazole Anticancer Antimicrobial Claisen–Schmidt reaction Introduction Cancer is the worldwide health problem and the most frightening disease of human (Zhang, 2002). Chemotherapy, Y. Rajendra Prasad AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, Andhra Pradesh, India e-mail: [email protected] G. V. S. Kumar (&) Department of Medicinal Chemistry, St John’s Pharmacy College, 6, 2nd Stage Vijaynagar, R.P.C.Layout, Bangalore 560040, Karnataka, India e-mail: [email protected] S. M. Chandrashekar Poornaprajna Institute of Scientific Research (PPISR), Poornaprajnapura, Bidalur, Devanahalli, Near Woodrich Resort, Bangalore 562110, Karnataka, India e-mail: [email protected]
either alone or as an adjunct to radiotherapy or surgery remains the treatment of choice in most of the cancers (Buolamwini, 1999; MacDonald, 2009). The current anticancer agents are mostly broad acting cytotoxic drugs. They impact structure and function of the rapidly proliferating cancer cells and arrest the cell cycle at a specific phase depending on the mechanism of action of the agents (Li et al., 2001; Engel et al., 2003). Due to their lack in specificity and adverse effects related to impact on rapidly dividing non-cancerous cells, there is an urgent need for identification of novel, potent, selective, and less toxic agents, which can overcome cancer resistance to drug treatment that has made many of the currently available chemotherapeutic agents ineffective (Borowski et al., 2005). The a,b-unsaturated ketones (chalcones) are considered to be precursors of flavonoids and isoflavonoids, found as naturally occurring compounds, but it could be considered that their true importance is extended in two branches. The biological activity associated with them, including antiinflammatory (Hsieh et al., 2000; De Leon et al., 2003), antipyretic (Mukherjee et al., 2001), anti invasive (Park et al., 1998), anticancer
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