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


Inceler N., Yilmaz A., BAYTAŞ S.

MEDICINAL CHEMISTRY RESEARCH, vol.22, no.7, pp.3109-3118, 2013 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 22 Issue: 7
  • Publication Date: 2013
  • Doi Number: 10.1007/s00044-012-0317-2
  • Journal Name: MEDICINAL CHEMISTRY RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3109-3118
  • Keywords: Synthesis, Anticancer activity, 1H-Pyrazoles, Thiophene, MTT, PRELIMINARY BIOLOGICAL EVALUATION, LUNG-CANCER CELLS, RAPID COLORIMETRIC ASSAY, PYRAZOLE DERIVATIVES, ANTITUMOR-ACTIVITY, BREAST-CANCER, AGENTS, APOPTOSIS, DISCOVERY, GROWTH
  • Gazi University Affiliated: Yes

Abstract

A series of novel thiophene containing 1,3-diarylpyrazole derivatives were synthesized and the structures were determined by IR, H-1-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 (GI(50) 25.2 +/- A 3.2 and 28.3 +/- A 1.53 mu M, respectively). Compound 4f, 4-trifluoromethylphenyl piperazine at the amide part, also showed potent activity on Raji and HL60 cancer cell lines with a GI(50) value of 32.0 +/- A 1.27 and 36.7 +/- A 2.15 mu M, 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.