72292-62-7Relevant academic research and scientific papers
New 1,2,4-triazole/pyrazole hybrids linked to oxime moiety as nitric oxide donor celecoxib analogs: Synthesis, cyclooxygenase inhibition anti-inflammatory, ulcerogenicity, anti-proliferative activities, apoptosis, molecular modeling and nitric oxide release studies
Abdellatif, Khaled R. A.,Elshaier, Yaseen A. M. M.,Fadaly, Wael A. A.,Hassanein, Emad H. M.
, (2020/03/27)
Two new series of hybrid structures 16a-f and 19a-f containing 1,2,4-triazole moiety, pyrazole core with COX-2 pharmacophore and oxime as NO donor moiety were designed, synthesized and evaluated for anti-inflammatory, cytotoxic activities and NO release. All compounds were more selective for COX-2 isozyme especially the sulphamoyl derivatives (16b, 16e, 19b and 19e) had COX-2 selectivity indexes (S.I. = 9.78, 8.57, 10.78 and 10.47 respectively) in comparison to celecoxib (S.I. = 8.68). Similarly, 16b, 16e, 19b and 19e were the most potent anti-inflammatory derivatives with ED50 = 46.98–54.45 μmol/kg better than celecoxib (ED50 = 76.09 μmol/kg). Also, 16b, 16e, 19b and 19e were significantly less ulcerogenic (ulcer indexes = 2.79–3.95) upon comparison with ibuprofen (ulcer index = 20.25) and comparable with celecoxib (ulcer index = 2.93). Regarding anti-cancer activity, most of the target derivatives 16a-f and 19a-f showed good activities against A-549, MCF-7, HCT-116 and PC-3 cancer cell lines. Additionally, these derivatives examined against F180 fibroblasts to investigate their selectivity indexes. The sulphamoyl derivatives with internal oxime 19b and 19e were the most potent derivatives against all used cell lines especially PC-3 (IC50 = 1.48 and 0.33 μM respectively) with 11.75 and 39.4-fold respectively selectivity towards PC-3 than F180 fibroblasts. The mechanistic investigation of 19b and 19e revealed that both compounds arrested cell cycle at G2/M phase by 32.16 and 39.95 folds, up-regulated Bax expression by 6.83 and 14.52 folds and down-regulated the expression of the gene Bcl-2 by 0.57 and 0.36fold respectively. Also, 19b and 19e were good inhibitor for p38MAPK (0.65 for 19b and 0.58 for 19e) and VEGFR-2 (0.39 for 19b and 0.54 for 19e) in comparison with PC-3 control cell. All compounds 16a-f and 19a-f released NO in a slow rate (0.15–3.17%) and the four sulphamoyl derivatives 16b, 16e, 19b and 19e were the most NO releasers (3.06, 2.15, 3.17 and 2.54% respectively). Docking studies were carried out to explain the interaction of 16a-f and 19a-f with the target enzymes. Docking mode of final designed compounds with celecoxib (ID: 3LN1) represented that their triazole ring adopted as the core aryl in Y shaped structure. Regarding EGFR inhibition, docking was carried out with ID: 1M17. The internal oxime serious was more active as anticancer because of their ability to form extra HBs with receptor cleft.
Synthesis and pharmacological evaluation of new pyrazolyl benzenesulfonamides linked to polysubstituted pyrazoles and thiazolidinones as anti-inflammatory and analgesic agents
Ashour, Hayam M. A.,El-Ashmawy, Ibrahim M.,Bayad, Aida E.
, p. 605 - 618 (2016/03/19)
New compounds comprising the pyrazolyl benzenesulfonamide scaffold linked to polysubstituted pyrazoles and thiazolidinones were synthesized and evaluated for their anti-inflammatory and analgesic activities. The results revealed that most of the compounds
Isatin-pyrazole benzenesulfonamide hybrids potently inhibit tumor-associated carbonic anhydrase isoforms IX and XII
Ibrahim, Hany S.,Abou-Seri, Sahar M.,Tanc, Muhammet,Elaasser, Mahmoud M.,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
, p. 583 - 593 (2015/10/19)
New series of benzenesulfonamide derivatives incorporating pyrazole and isatin moieties were prepared using celecoxib as lead molecule. Biological evaluation of the target compounds was performed against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more precisely against the human isoforms hCA I, II (cytosolic), IX and XII (transmembrane, tumor-associated enzymes). Most of the tested compounds efficiently inhibited hCA I, II and IX, with KIs of 2.5-102 nM, being more effective than the reference drug acetazolamide. Compounds 11e, 11f, 16e and 16f were found to inhibit hCA XII with Ki of 3.7, 6.5, 5.4 and 7.2 nM, respectively. Compounds 11e and 16e, with 5-NO2substitution on the isatin ring, were found to be selective inhibitors of hCA IX and hCA XII. Docking studies revealed that the NO2group of both compounds participate in interactions with Asp132 within the hCA IX active site, and with residues Lys67 and Asp130 in hCA XII, respectively.
Synthesis and biological evaluation of novel pyrazoles and pyrazolo[3,4-d]pyrimidines incorporating a benzenesulfonamide moiety
Ashour, Hayam M. A.,Wahab, Abeer E. Abdel
scheme or table, p. 238 - 252 (2009/05/27)
Synthesis and biological evaluation of novel pyrazoles and pyrazolo[3,4-d]pyrimidines are reported. Fourteen compounds were selected by the NCI and tested for their preliminary in-vitro anticancer activity, whereas all the synthesized compounds were evalu
