Pharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Bioorg Chem. 2018 Apr;77:38-46. doi: 10.1016/j.bioorg.2017.12.028. Epub 2018 Jan 4.
New thienopyrimidinone and triazolothienopyrimidinone derivatives have been synthesized. These compounds were subjected to anti-inflammatory and antimicrobial activity screening aiming to identify new candidates that have dual anti-inflammatory and antimicrobial activities. Compounds 5, 7 and 10a showed minimal ulcerogenic effect and high selectivity towards human recombinant COX-2 over COX-1 enzyme. Their docking outcome correlated with their biological activity and assured the high selectivity binding towards COX-2. In addition, they could act safely up to 80 mg/kg orally or 40 mg/kg parentrally. The antimicrobial screening showed that compound 10a displayed distinctive inhibitory effect on the growth of Escherichia coli comparable to that of ampicillin. Moreover, compounds 5, 7, 9 and 12a possessed 50% of the inhibitory activity of ampicillin against E. coli. Thus, compounds 5, 7 and 10a represent promising dual acting anti-inflammatory and antimicrobial agents. This work provides rewarding template enriching the chemical space for dual anti-inflammatory anti-microbial activities.
新型噻吩并嘧啶酮和三唑并噻吩并嘧啶酮衍生物已被合成。这些化合物进行了抗炎和抗菌活性筛选，旨在寻找具有双重抗炎和抗菌活性的新候选物。化合物 5、7 和 10a 表现出最小的致溃疡作用和对人重组 COX-2 酶相对于 COX-1 酶的高选择性。它们的对接结果与它们的生物学活性相关联，并确保了对 COX-2 的高选择性结合。此外，它们的口服剂量高达 80mg/kg 或 40mg/kg 时是安全的。抗菌筛选表明，化合物 10a 对大肠杆菌的生长表现出独特的抑制作用，与氨苄青霉素相当。此外，化合物 5、7、9 和 12a 对大肠杆菌的抑制活性为氨苄青霉素的 50%。因此，化合物 5、7 和 10a 代表了有前途的双重作用抗炎和抗菌药物。这项工作提供了有价值的模板，丰富了具有双重抗炎和抗菌活性的化学空间。
