Al-Khalifa Saleh E, Jennings Megan C, Wuest William M, Minbiole Kevin P C
Department of Chemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA, 19085, USA.
Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
ChemMedChem. 2017 Feb 20;12(4):280-283. doi: 10.1002/cmdc.201600546. Epub 2017 Jan 26.
A series of 18 bis- and tris-pyridinium amphiphiles were prepared and tested for both antimicrobial activity and lytic capability, in comparison with the commercially available pyridinium antiseptic cetylpyridinium chloride (CPC). Assessments were made against Gram-positive and Gram-negative bacteria, including two methicillin-resistant Staphylococcus aureus (MRSA) strains. While 2Pyr-11,11 was identified as one of the most potent antimicrobial quaternary ammonium compounds (QACs) reported to date, boasting nanomolar inhibition against five of six bacteria tested, no significant improvement in bioactivity of tris-pyridinium amphiphiles over their bis-pyridinium counterparts was observed. However, the multicationic QACs (multiQACs) presented herein did display significant advantages over the monocationic CPC; while similar red blood cell lysis was observed, superior activity against both Gram-negative bacteria and resistant S. aureus strains led to the discovery of four pyridinium-based multiQACs with advantageous therapeutic indices.
制备了一系列18种双吡啶和三吡啶两亲物，并测试了它们的抗菌活性和裂解能力，同时与市售的吡啶类防腐剂十六烷基氯化吡啶（CPC）进行比较。对革兰氏阳性菌和革兰氏阴性菌进行了评估，包括两株耐甲氧西林金黄色葡萄球菌（MRSA）菌株。虽然2Pyr-11,11被确定为迄今为止报道的最有效的抗菌季铵化合物（QACs）之一，对所测试的六种细菌中的五种具有纳摩尔抑制作用，但未观察到三吡啶两亲物的生物活性比其二吡啶对应物有显著提高。然而，本文介绍的多阳离子QACs（multiQACs）确实比单阳离子CPC具有显著优势；虽然观察到类似的红细胞裂解现象，但对革兰氏阴性菌和耐药金黄色葡萄球菌菌株的卓越活性导致发现了四种具有有利治疗指数的吡啶基multiQACs。
