Drug-resistant pathogens are a major cause of hospital- and community-associated bacterial infections in the United States and around the world. These infections are increasingly difficult to treat due to the development of antibiotic resistance and the formation of bacterial biofilms. In the paper, a series of phenazines were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive (methicillin resistant staphylococcus aureus, MRSA) and Gram negative (Escherichia coli, E. coli) bacteria. The compound 6,9-dichloro-N-(methylsulfonyl)phenazine-1-carboxamide (18c) proved to be the most active molecule (MIC = 16 μg/mL) against MRSA whereas 9-methyl-N-(methylsulfonyl)phenazine-1-carboxamide (30e) showed good activity against both MRSA (MIC = 32 μg/mL) and E. coli (MIC = 32 μg/mL). Molecule 18c also demonstrated significant biofilm dispersion and inhibition against S. aureus. Preliminary studies indicate the molecules do not disturb bacterial membranes and there activity is not directly linked to the generation of reactive oxygen species. Compound 18c displayed minor toxicity against mammalian cells. Metabolic stability studies of the most promising compounds indicate stability towards phase I and phase II metabolizing enzymes.

耐药病原体是在美国和世界范围内与医院和社区相关的细菌感染的主要原因。由于抗生素耐药性的发展和细菌生物膜的形成，这些感染越来越难以治疗。在本文中，合成了一系列吩嗪并评估了它们对革兰氏阳性（耐甲氧西林金黄色葡萄球菌，MRSA）和革兰氏阴性（大肠杆菌，大肠杆菌）细菌的体外抗菌活性。化合物6,9-二氯-N-（甲基磺酰基）吩嗪-1-羧酰胺（18c）被证明是对抗MRSA活性最高的分子（MIC = 16μg/ mL），而9-甲基-N-N-（甲基磺酰基）吩嗪-1-羧酰胺（30e）对MRSA（MIC = 32μg/ mL）和大肠杆菌（MIC = 32μg/ mL）均显示出良好的活性。分子18c还表现出明显的生物膜分散性和对金黄色葡萄球菌的抑制作用。初步研究表明，该分子不会干扰细菌膜，并且活性与活性氧的产生没有直接关系。化合物18c对哺乳动物细胞显示出较小的毒性。对最有前途的化合物的代谢稳定性研究表明，其对I和II期代谢酶具有稳定性。