Liebens Veerle, Gerits Evelien, Knapen Wouter J, Swings Toon, Beullens Serge, Steenackers Hans P, Robijns Stijn, Lippell Anna, O'Neill Alex J, Veber Matija, Fröhlich Mirjam, Krona Annika, Lövenklev Maria, Corbau Romu, Marchand Arnaud, Chaltin Patrick, De Brucker Katrijn, Thevissen Karin, Cammue Bruno P, Fauvart Maarten, Verstraeten Natalie, Michiels Jan
Bioorg Med Chem Lett. 2014 Dec 1;24(23):5404-8. doi: 10.1016/j.bmcl.2014.10.039.
Pseudomonas aeruginosa strains resistant towards all currently available antibiotics are increasingly encountered, raising the need for new anti-pseudomonal drugs. We therefore conducted a medium-throughput screen of a small-molecule collection resulting in the identification of the N-alkylated 3,6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol (MIC = 18.5 μg mL⁻¹). This compound, compound 1, is bacteriostatic towards a broad spectrum of Gram-positive and Gram-negative pathogens, including P. aeruginosa. Importantly, 1 also eradicates mature biofilms of P. aeruginosa. 1 displays no cytotoxicity against various human cell types, pointing to its potential for further development as a novel antibacterial drug.
对目前所有可用抗生素均耐药的铜绿假单胞菌菌株越来越常见,这就需要研发新的抗铜绿假单胞菌药物。因此,我们对一个小分子化合物库进行了中等通量筛选,结果鉴定出了N-烷基化的3,6-二卤代咔唑1-(仲丁基氨基)-3-(3,6-二氯-9H-咔唑-9-基)丙-2-醇(MIC = 18.5 μg mL⁻¹)。该化合物,即化合物1,对包括铜绿假单胞菌在内的多种革兰氏阳性和革兰氏阴性病原体具有抑菌作用。重要的是,1还能根除铜绿假单胞菌的成熟生物膜。1对多种人类细胞类型均无细胞毒性,表明其有作为新型抗菌药物进一步开发的潜力。