This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles. The hybridized target molecules were characterized by 1H NMR, 13C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 μg/mL. The active molecule 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramolecular complex, which might be responsible for its antimicrobial action. The further investigation showed that this molecule could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force.

中文翻译：

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新型潜在的多目标抗微生物氨基磺酰胺类嘧啶和吡咯类化合物的组合设计和生物学评估。

这项工作探索了一种新型的潜在的多目标抗微生物三成分磺胺酰胺嘧啶和吡咯类化合物的组合。杂交的靶分子通过1 H NMR，13 C NMR和HRMS光谱表征。与参考药物诺氟沙星和氟康唑相比，一些已开发的目标化合物发挥了有希望的抗菌活性。值得注意的是，磺胺与嘧啶和吲哚的杂化物5c可以有效抑制粪肠球菌的生长，其MIC值为1μg/ mL。活性分子5c显示出低细胞毒性，并且没有明显触发对被测细菌菌株的抗药性。机理研究表明，化合物5c不仅可以发挥有效的膜渗透性，而且还可以插入抗性E的DNA中。粪便形成5c-DNA超分子复合物，这可能是其抗菌作用的原因。进一步的研究表明，人血清白蛋白可以通过氢键和范德华力有效地转运该分子。