Ferreira Bianca da S, de Almeida Angelina M, Nascimento Thiago C, de Castro Pedro P, Silva Vania L, Diniz Claúdio G, Le Hyaric Mireille
Departamento de Química, ICE, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
Departamento de Parasitologia, Microbiologia e Imunologia, ICB, Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
Bioorg Med Chem Lett. 2014 Oct 1;24(19):4626-4629. doi: 10.1016/j.bmcl.2014.08.047. Epub 2014 Aug 30.
In continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and for their antifungal activity against four species of Candida (C. albicans, C. tropicalis, C. glabrata and C. parapsilosis). Compounds 5a (N-(2-aminoethyl)dodecanamide), 5b (N-(2-aminoethyl)tetracanamide) and 6d (N-(3-aminopropyl)oleamide) were the most active against Gram-positive bacteria, with MIC values ranging from 1 to 16μg/mL and were evaluated for their activity against 21 clinical isolates of methicillin-resistant S. aureus. All the compounds exhibited good to moderate antifungal activity. Compared to chloramphenicol, compound 6b displayed a similar activity (MIC50=16μg/mL). A positive correlation could be established between lipophilicity and biological activity.
为继续寻找新的抗菌化合物，我们以脂肪酸甲酯与1,2 - 乙二胺、1,3 - 丙二胺或1,4 - 丁二胺为原料制备了一系列脂肪族N - 酰基二胺。对合成的化合物针对革兰氏阳性菌（金黄色葡萄球菌、表皮葡萄球菌）、革兰氏阴性菌（大肠杆菌、铜绿假单胞菌）的抗菌活性以及针对四种念珠菌（白色念珠菌、热带念珠菌、光滑念珠菌和近平滑念珠菌）的抗真菌活性进行了筛选。化合物5a（N - (2 - 氨基乙基)十二酰胺）、5b（N - (2 - 氨基乙基)十四酰胺）和6d（N - (3 - 氨基丙基)油酰胺）对革兰氏阳性菌活性最强，最低抑菌浓度（MIC）值在1至16μg/mL范围内，并对其针对21株耐甲氧西林金黄色葡萄球菌临床分离株的活性进行了评估。所有化合物均表现出良好至中等的抗真菌活性。与氯霉素相比，化合物6b表现出相似的活性（MIC50 = 16μg/mL）。亲脂性与生物活性之间可建立正相关关系。
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