Synthesis, cytotoxicity, and molecular properties prediction of novel 1,3-diarylpyrazole derivatives
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Med Chem Res (2013) 22:4893–4908 DOI 10.1007/s00044-013-0505-8
ORIGINAL RESEARCH
Synthesis, cytotoxicity, and molecular properties prediction of novel 1,3-diarylpyrazole derivatives Sultan Nacak Baytas • Nazan Inceler Akın Yılmaz
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Received: 8 November 2012 / Accepted: 17 January 2013 / Published online: 31 January 2013 Ó Springer Science+Business Media New York 2013
Abstract A novel combinatorial library of ester and amide derivatives of 1,3-diarylpyrazoles was designed and synthesized. Anticancer activities of these compounds were assessed against MCF7, MDA-MB-231, HeLa, Raji, and HL60 human cancer cells by MTT assay. Out of these, compounds 4c and 5f were found as the most promising anticancer agents with IC50 values of 8.12 and 9.63 lM in Raji cells, respectively. All compounds exhibited suitable drug-like characteristics according to Lipinski’s rule. Keywords Synthesis Anticancer activity 1H-Pyrazoles Pyridine MTT
Introduction Cancer is the second leading cause of death in developed countries, accounting for nearly one in five deaths. Chemotherapy is a major form of cancer treatment. However, majority of cancers are either resistant to chemotherapy or acquire resistance during treatment. Several important drugs including 5-flurouracil (5FU), doxorubicin, celecoxib, and mitoxantrone with different structures and mechanisms of antitumor activities, fail to end these
S. N. Baytas (&) N. Inceler Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey e-mail: [email protected]; [email protected] A. Yılmaz Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06500 Bes¸ evler, Ankara, Turkey
problems completely. Due to several side effects, drug resistance and failure of antitumor drugs in certain cases of cancer, the design and discovery of non-traditional, efficient and safe chemical classes of agents are prime targets in contemporary medicinal chemistry (Cozzi, 2003; Johnston et al., 2005). A key feature of cancer cells is their uncontrolled proliferation, thus, inhibition of proliferative pathways is believed to be an effective strategy to fight cancer and much attention has recently been paid to the discovery and development of new, more selective anticancer agents. Pyrazoles constitute an important heterocyclic family containing nitrogen in their five-membered ring. Several pyrazole derivatives have been found to possess considerable biological activities, which have stimulated numerous research activities in medicinal chemistry or chemical biology (Silveira et al., 1993; Sridhar et al., 2004; Nagarapu et al., 2011; Padmaja et al., 2009; Gaston et al., 1996, Baytas et al., 2012; Banoglu et al., 2007). Many pyrazole derivatives are well acknowledged to possess a wide range of anticancer bioactivities (Riyadh et al., 2010; Anzaldi et al., 2009; El-Shafei et al., 2009; Zheng et al., 2010; Xie et al., 2010; Lian et al., 2009). The literature survey has revealed that some pyrazoles
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