title: 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: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
authors: Kaan
authors: K
authors: Kucukoglu
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
authors: Fatih
authors: F
authors: Oral
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
authors: Tevfik
authors: T
authors: Aydin
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
authors: Cem
authors: C
authors: Yamali
authors: b Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Mersin University , Mersin , Turkey.
authors: Oztekin
authors: O
authors: Algul
authors: c Division of Pharmacology , School of Dentistry, Meikai University School of Dentistry , Sakado , Saitama , Japan.
authors: Hiroshi
authors: H
authors: Sakagami
authors: d Department of Chemistry , Faculty of Science, Ataturk University , Erzurum , Turkey.|e Department of Zoology , College of Science, King Saud University , Riyadh , Saudi Arabia , and.
authors: Ilhami
authors: I
authors: Gulcin
authors: f Neurofarba Departmente Laboratorio di ChimicaBioinorganica, Universita degli Studi di Firenze , via U. Schiff 6, SestoFiorentino (Florence ), Italy.
authors: Claudiu T
authors: CT
authors: Supuran
authors: a Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
authors: Halise Inci
authors: HI
authors: Gul
mesh_terms: D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D011720:Pyrazoles; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Carbonic anhydrase; cytotoxicity; dental cells; pyrazoline; sulfonamide; tumor selectivity