Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM, CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Laboratorio de Patógenos Bacterianos Intracelulares, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB, CSIC), Darwin 3, 28049 Madrid, Spain.
Molecules. 2018 Jun 22;23(7):1513. doi: 10.3390/molecules23071513.
Cationic and non-peptide small molecules containing a total of six positive charges arranged on one side and a long aliphatic tail on the other have been synthesized and tested against Gram-positive and Gram-negative bacteria. The positive charges have been contributed by two aminophenol residues. These molecules have showed remarkable antimicrobial activity against Gram-positive bacteria including multidrug-resistant strains. Our structure⁻activity relationship studies demonstrated the importance of the length and flexibility of the hydrophobic tail for the antimicrobial activity. Importantly, these compounds are non-toxic to eukaryotic cells at the concentration affecting growth in bacteria, reflecting an acceptable margin of safety. The small size and easy synthetic accessibility of our molecules can be of interest for the further development of novel antimicrobials against Gram-positive bacterial pathogens, including multidrug-resistant strains.
已合成并测试了带有总共六个正电荷的阳离子和非肽小分子，这些正电荷排列在一侧，另一侧带有长脂肪链尾巴。正电荷由两个氨基酚残基提供。这些分子对革兰氏阳性菌（包括多药耐药株）表现出显著的抗菌活性。我们的结构-活性关系研究表明，疏水尾巴的长度和灵活性对抗菌活性很重要。重要的是，这些化合物在影响细菌生长的浓度下对真核细胞无毒，反映出可接受的安全裕度。我们的分子具有小尺寸和易于合成的特点，这可能对进一步开发针对革兰氏阳性细菌病原体（包括多药耐药株）的新型抗菌药物具有重要意义。
