Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines


Kucukoglu K., Oral F., Aydin T., Yamali C. , Algul O., Sakagami H., ...More

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.31, pp.20-24, 2016 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31
  • Publication Date: 2016
  • Doi Number: 10.1080/14756366.2016.1217852
  • Title of Journal : JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Page Numbers: pp.20-24
  • Keywords: Carbonic anhydrase, cytotoxicity, dental cells, pyrazoline, sulfonamide, tumor selectivity, BEARING BENZENE SULFONAMIDE, DERIVATIVES, ANTICANCER, IX, ENZYME, DRUGS, XII

Abstract

A series of polymethoxylated-pyrazoline benzene sulfonamides were synthesized, investigated for their cytotoxic activities on tumor and non-tumor cell lines and inhibitory effects on carbonic anhydrase isoenzymes (hCA I and hCA II). Although tumor selectivity (TS) of the compounds were less than the reference compounds 5-Fluorouracil and Melphalan, trimethoxy derivatives 4, 5, and 6 were more selective than dimethoxy derivatives 2 and 3 as judged by the cytotoxicity assay with the cells both types originated from the gingival tissue. The compound 6 (443-(4-methonipheny1)-5-(3,4,5-trimethoxypheny1)-4,5-dihydro-1H-pyrazol-1-yl] benzene sulfonamide) showed the highest TS values and can be considered as a lead molecule of the series for further investigations. All compounds synthesized showed superior CA inhibitory activity than the reference compound acetazolamide on hCA I, and II isoenzymes, with inhibition constants in the range of 26.5-55.5 nM against hCA I and of 18.9-28.8 nM against hCA II, respectively.