Synthesis, evaluation and modeling of some triazolothienopyrimidinones as anti-inflammatory and antimicrobial agents

被引：16

作者：

Bekhit, Adnan A. ^{[1
]}

Farghaly, Ahmed M. ^{[1
]}

Shafik, Ragab M. ^{[1
]}

Elsemary, Mona Ma ^{[1
]}

El-Shoukrofy, Mai S. ^{[1
]}

Bekhit, Alaa El-Din A. ^{[2
]}

Ibrahim, Tamer M. ^{[3
,4
]}

机构：

[1] Alexandria Univ, Fac Pharm, Pharmaceut Chem Dept, Alexandria 21521, Egypt

[2] Univ Otago, Food Sci, Dunedin, New Zealand

[3] Kafrelsheikh Univ, Fac Pharm, Pharmaceut Chem Dept, Kafr Al Sheikh 33516, Egypt

[4] Heliopolis Univ Sustainable Dev, Fac Pharm & Drug Technol, Pharmaceut Chem Dept, Cairo 11777, Egypt

来源：

FUTURE MEDICINAL CHEMISTRY | 2017年 / 9卷 / 09期

关键词：

dual anti-inflammatory antimicrobial activities; human COX-1 and COX-2 enzymatic assay; molecular modeling studies; pyrazole; triazolothienopyrimidinone derivatives; PROTEIN-LIGAND DOCKING; DNA GYRASE INHIBITORS; BIOLOGICAL EVALUATION; GENETIC ALGORITHM; CYCLOOXYGENASE-2; INHIBITORS; SELECTIVE-INHIBITION; DERIVATIVES; DESIGN; THIENOPYRIMIDINES; PYRAZOLE;

D O I：

10.4155/fmc-2016-0242

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: New triazolotetrahydrobenzothienopyrimidinone derivatives were synthesized. Experimental: Their structures were confirmed, and their anti-inflammatory, antimicrobial activities and ulcerogenic potentials were evaluated. Results: Compounds 7a, 10a and 11a showed minimal ulcerogenic effect and high selectivity toward human recombinant COX-2 over COX-1 enzyme with IC50 values of 1.39, 1.22 and 0.56 mu M, respectively. Their docking outcome correlated with their biological activity and confirmed the high selectivity binding toward COX-2. Compound 12b displayed antimicrobial activity comparable to that of ampicillin against Escherichia coli while compounds 6 and 11c were similar to ampicillin against Staphylococcus aureus. In addition, compounds 7a, 9a, 10b and 11c showed dual anti-inflammatory/antimicrobial activities. Conclusion: This work represents a promising matrix for developing new potential anti-inflammatory, antimicrobial and dual antimicrobial/anti-inflammatory candidates.

引用

页码：881 / 897

页数：17

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