新合成喹唑啉衍生物的分子建模、酶活性、抗炎和抗关节炎活性
Molecular modeling, enzyme activity, anti-inflammatory and antiarthritic activities of newly synthesized quinazoline derivatives.
作者信息
Abuelizz Hatem A, Hassane Anouar El, Marzouk Mohamed, Ezzeldin Essam, Ali Azza A, Al-Salahi Rashad
机构信息
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Department of Chemistry, College of Science & Humanities, Prince Sattam Bin Abdulaziz University, 83 Al-Kharj, Saudi Arabia.
出版信息
Future Med Chem. 2017 Nov;9(17):1995-2009. doi: 10.4155/fmc-2017-0157. Epub 2017 Aug 9.
AIM
16 thioxoquinazolines were evaluated in vivo for anti-inflammatory activity using carrageenan-induced paw edema assay.
RESULTS
In particular, out of the targets (1-16), compounds 4 and 6 displayed the highest anti-inflammatory activity (≥80%) and furtherly tested against complete Freund's adjuvant-induced arthritic rats. Significant reduction in the serum level of IL-1β, COX-2 and prostaglandin E2 in the complete Freund's adjuvant rats is demonstrated by compounds 4 and 6. Furthermore, compound 4 showed non-selective activity against COX-1 and COX 2, however, compound 6 was specific toward COX-2. Molecular docking study has demonstrated the possible binding modes of the active quinazolines 4 and 6 in the COX-2 active site.
CONCLUSION
These targets could be used as templates for further development of new derivatives with potent anti-inflammatory activity.
目的
使用角叉菜胶诱导的爪肿胀试验，在体内评估16种硫代喹唑啉的抗炎活性。
结果
特别是在目标化合物（1 - 16）中，化合物4和6表现出最高的抗炎活性（≥80%），并进一步针对完全弗氏佐剂诱导的关节炎大鼠进行了测试。化合物4和6证明可显著降低完全弗氏佐剂大鼠血清中IL - 1β、COX - 2和前列腺素E2的水平。此外，化合物4对COX - 1和COX - 2表现出非选择性活性，然而，化合物6对COX - 2具有特异性。分子对接研究表明了活性喹唑啉4和6在COX - 2活性位点的可能结合模式。
结论
这些目标化合物可作为模板用于进一步开发具有强效抗炎活性的新衍生物。
Zotero 插件