Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds
Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds
复制标题
DOI：
10.1016/j.ejmech.2014.08.016
复制
发表时间：
2014-10-06
影响因子：
6.7
通讯作者：
Abdel-Aziz, Marwa M.
中科院分区：
文献类型：
--
作者：
Ibrahim, Hany S.;Eldehna, Wagdy M.;Abdel-Aziz, Marwa M.
RAB 15是一种先导抗菌剂，其中甲氧苄啶与酞嗪部分连接。同样，我们在这项研究中的策略取决于一些磺胺类药物和某些酞嗪-1（2 H）-酮支架之间的相互联系，试图提高其抗菌活性。该方法通过4-取代的酞嗪-1（2 H）-酮9a、B或14 a、B与磺胺1a、磺胺噻唑1B或磺胺嘧啶1c通过酰胺连接基6a、B组合来实现，以分别产生目标化合物10 a-d和15 a-e。新合成的化合物的抗菌活性表明，所有测试化合物的抗菌活性均高于其参比磺胺类药物1a-c。化合物10 c对革兰氏阳性菌肺炎链球菌和金黄色葡萄球菌的抗菌活性最高，MIC = 0.39 μ mol/mL。此外，化合物10 d对革兰氏阴性菌大肠杆菌和鼠伤寒沙门氏菌显示出优异的抗菌活性，MIC分别为0.39和0.78 μ mol/mL。(C)2014年Elsevier Masson SAS。All rights reserved.
RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 mu mol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella Lyphimurium with MIC = 0.39 and 0.78 mu mol/mL, respectively. (C) 2014 Elsevier Masson SAS. All rights reserved.