Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines.

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 (4-[3-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-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.

• Authors: Kaan Kucukoglu, Fatih Oral, Tevfik Aydin, Cem Yamali, Oztekin Algul, Hiroshi Sakagami, Ilhami Gulcin, Claudiu T Supuran, Halise Inci Gul
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 31 Issue sup4 Pg. 20-24 ( 2016) ISSN: 1475-6374 [Electronic] England
• PMID: 27579806 (Publication Type: Journal Article)

Chemical References

• Carbonic Anhydrase Inhibitors
• Pyrazoles
• Carbonic Anhydrase I
• Carbonic Anhydrase II

Topics

• Carbonic Anhydrase I (antagonists & inhibitors, metabolism)
• Carbonic Anhydrase II (antagonists & inhibitors, metabolism)
• Carbonic Anhydrase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Molecular Structure
• Pyrazoles (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship