Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, Southwest University, Chongqing 400715, PR China.
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, Southwest University, Chongqing 400715, PR China.
Bioorg Med Chem Lett. 2021 Jun 1;41:127995. doi: 10.1016/j.bmcl.2021.127995. Epub 2021 Mar 26.
A class of structurally unique para-aminobenzenesulfonyl oxadiazoles as new potential antimicrobial agents was designed and synthesized from acetanilide. Some target para-aminobenzenesulfonyl oxadiazoles showed antibacterial potency. Noticeably, hexyl derivative 8b (MIC = 1 μg/mL) was more active than norfloxacin against drug resistant MRSA. Compound 8b was able to disturb the membrane effectively and intercalate into deoxyribonucleic acid (DNA) to form a steady 8b-DNA complex, which might be responsible for bacterial metabolic inactivation. Molecular docking indicated that 8b could interact with DNA topoisomerase IV through noncovalent interactions to form a supramolecular complex and hinder the function of this enzyme. These results indicated that hexyl derivative 8b deserved further investigation as a new lead compound.
一类结构独特的对氨基苯磺酰基噁二唑类化合物被设计并合成出来，它们是从乙酰苯胺衍生而来的新型潜在抗菌剂。一些目标对氨基苯磺酰基噁二唑类化合物表现出抗菌活性。值得注意的是，己基衍生物 8b（MIC = 1 μg/mL）对耐药性 MRSA 的活性比诺氟沙星更强。化合物 8b 能够有效地扰乱细胞膜，并插入脱氧核糖核酸（DNA）中形成稳定的 8b-DNA 复合物，这可能是导致细菌代谢失活的原因。分子对接表明，8b 可以通过非共价相互作用与 DNA 拓扑异构酶 IV 相互作用形成超分子复合物，从而阻碍该酶的功能。这些结果表明，己基衍生物 8b 值得进一步研究，作为一种新的先导化合物。
