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Synthesis of ester and amide derivatives of 1-phenyl-3-(thiophen-3-yl)-1H-pyrazole-4-carboxylic acid and study of their anticancer activity

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Abstract

A series of novel thiophene containing 1,3-diarylpyrazole derivatives were synthesized and the structures were determined by IR, 1H-NMR, and HRMS analysis. The anticancer activity of the title compounds against MCF7, MDA-MB-231, HeLa, Raji, and HL60 human cancer cells growth were investigated by MTT assay. Interestingly, Raji and HL60 cells exhibited more sensitivity to synthesized compounds. (4-Benzyl-piperidin-1-yl)-(1-phenyl-3-thiophen-3-yl-1H-pyrazol-4-yl)-methanone (4c) possessed the highest growth inhibitory effect on Raji and HL60 cancer cells (GI50 25.2 ± 3.2 and 28.3 ± 1.53 μM, respectively). Compound 4f, 4-trifluoromethylphenyl piperazine at the amide part, also showed potent activity on Raji and HL60 cancer cell lines with a GI50 value of 32.0 ± 1.27 and 36.7 ± 2.15 μM, respectively. Physicochemical properties of the synthesized compounds were evaluated in silico, and it was found that all compounds should present good passive oral absorption. All synthesized compounds demonstrated good drug-likeness values. The data suggested that these compounds might be promising for further development.

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Acknowledgments

This investigation was partially supported by Scientific Research Grant 02/2011-08, awarded by Gazi University BAP.

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  1. Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara, Turkey

    Nazan Inceler & Sultan Nacak Baytas

  2. Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Beşevler, 06500, Ankara, Turkey

    Akın Yılmaz

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  1. Nazan Inceler
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Inceler, N., Yılmaz, A. & Baytas, S.N. Synthesis of ester and amide derivatives of 1-phenyl-3-(thiophen-3-yl)-1H-pyrazole-4-carboxylic acid and study of their anticancer activity. Med Chem Res 22, 3109–3118 (2013). https://doi.org/10.1007/s00044-012-0317-2

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