Chen Ying-Ying, Gopala Lavanya, Bheemanaboina Rammohan R Yadav, Liu Han-Bo, Cheng Yu, Geng Rong-Xia, Zhou Cheng-He
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
ACS Med Chem Lett. 2017 Dec 1;8(12):1331-1335. doi: 10.1021/acsmedchemlett.7b00452. eCollection 2017 Dec 14.
A series of novel naphthalimide aminothiazoles were developed for the first time and evaluated for their antimicrobial activity. Some prepared compounds possessed good inhibitory activity against the tested bacteria and fungi. Noticeably, the piperazine derivative displayed superior antibacterial activity against MRSA and with MIC values of 4 and 8 μg/mL, respectively, to reference drugs. The most active compound showed low toxicity against mammalian cells with no obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy and efficient membrane permeability. Preliminarily investigations revealed that compound could not only bind with gyrase-DNA complex through hydrogen bonds but could effectively intercalate into MRSA DNA to form -DNA supramolecular complex, which might be responsible for the powerful bioactivity. Further transportation behavior evaluation indicated that molecule could be effectively stored and carried by human serum albumin, and the hydrophobic interactions and hydrogen bonds played important roles in the binding process.
首次开发了一系列新型萘二甲酰亚胺氨基噻唑，并对其抗菌活性进行了评估。一些制备的化合物对测试的细菌和真菌具有良好的抑制活性。值得注意的是，哌嗪衍生物对耐甲氧西林金黄色葡萄球菌（MRSA）表现出优异的抗菌活性，其最低抑菌浓度（MIC）值分别为4和8μg/mL，优于参考药物。活性最高的化合物对哺乳动物细胞毒性低，不会明显引发细菌耐药性的产生，并且还具有快速杀菌效果和高效的膜通透性。初步研究表明，该化合物不仅可以通过氢键与拓扑异构酶-DNA复合物结合，还可以有效地插入MRSA DNA中形成 -DNA超分子复合物，这可能是其强大生物活性的原因。进一步的转运行为评估表明，该分子可以被人血清白蛋白有效储存和携带，疏水相互作用和氢键在结合过程中起重要作用。
