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.

Synthesis of 2‐amino‐3‐cyanopyridine derivatives and investigation of their carbonic anhydrase inhibition effects

“…The hCA I isoenzyme is found in many tissues and occurs in high concentrations in the blood and gastrointestinal tract. It is involved in retinal and cerebral edema, and the inhibition of hCA I may be a valuable tool for fighting these conditions . CAIs are clinically used as diuretics, anticonvulsant, antiglaucoma, antiobesity, and antitumor agents for decades .…”

Synthesis, molecular modeling, and biological evaluation of 4‐[5‐aryl‐3‐(thiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazol‐1‐yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes

“…First, chalcones were synthesized via Claisen–Schmidt reaction as described in literatures . 2‐Acetylthiophene (2 g, 16 mmol) and the appropriate aromatic aldehyde (1.7 g for 1 , 2.0 g for 2 , 2.2 g for 3 , 2.0 g for 4 , 2.2 g for 5 , 3.0 g for 6 , 2.8 g for 7 , 1.8 g for 8 , 2.6 g for 9 , 2.6 g for 10, 16 mmol) were dissolved in ethanol (10 ml), and an aqueous solution of potassium hydroxide (10 ml, 40% w/v) was added dropwise into the reaction flask.…”

Characterization and inhibition effects of some metal ions on carbonic anhydrase enzyme from Kangal Akkaraman sheep

“…Following the purification of CA, SDS‐PAGE procedure was conducted in according to Laemmle's method as described previously . Stacking and running gels were composed of 3% and 10% acrylamide and 0.1% SDS, respectively …”