We describe the rational use of the neglected isocyano moiety as pharmacophoric group for the design of novel 4-isocyanophenylamides as antibacterial agents. This class of novel compounds showed to be highly effective against methicillin resistant Staphylococcus aureus strains. In particular, from an extensive screening, we identified compound 42 as lead compound. It has shown a potent antimicrobial activity, an additive effect with most antibiotics currently in use, the ability not to induce the formation of resistant strains after ten passages, and the ability to block the biofilm formation. A nontoxic profile on mammalian cells and a proper metabolic stability on human liver microsome complete the picture of this new weapon against methicillin resistant Staphylococcus aureus infections.

我们描述了被忽视的异氰基部分作为药效团的合理使用，用于设计新型 4-异氰基苯基酰胺作为抗菌剂。这类新型化合物显示出对耐甲氧西林金黄色葡萄球菌菌株非常有效。特别是，通过广泛筛选，我们将化合物42鉴定为先导化合物。它已显示出强大的抗菌活性、与目前使用的大多数抗生素的累加效应、十次传代后不诱导耐药菌株形成的能力以及阻断生物膜形成的能力。对哺乳动物细胞的无毒特性和对人类肝微粒体的适当代谢稳定性完善了这种抗甲氧西林抗药性的新武器金黄色葡萄球菌感染。