Vlainić Josipa, Kosalec Ivan, Pavić Kristina, Hadjipavlou-Litina Dimitra, Pontiki Eleni, Zorc Branka
a Laboratory for Advanced Genomics, Division of Molecular Medicine , Rudjer Bošković Institute , Zagreb , Croatia.
b Faculty of Pharmacy and Biochemistry, Department of Microbiology , University of Zagreb , Zagreb , Croatia.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):376-382. doi: 10.1080/14756366.2017.1423067.
Primaquine (PQ) ureidoamides 5a-f were screened for antimicrobial, biofilm eradication and antioxidative activities. Susceptibility of the tested microbial species towards tested compounds showed species- and compound-dependent activity. N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]-4-methylpentanamide (5a) and 2-(4-chlorophenyl)-N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]acetamide (5d) showed antibacterial activity against S. aureus strains (MIC = 6.5 µg/ml). Further, compounds 5c and 5d had weak antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. None of the tested compounds showed a wide spectrum of antifungal activity. In contrast, most of the compounds exerted strong activity in a biofilm eradication assay against E. coli, P. aeruginosa and Candida albicans, comparable to or even higher than gentamycin, amphotericin B or parent PQ. The most active compounds were 5a and 5b. Tested compounds were inactive against biofilm formation by C. parapsylosis, Enterococcus faecalis, C. tropicalis and C. krusei. Compounds 5b-f significantly inhibited lipid peroxidation (80-99%), whereas compound 5c presented interesting LOX inhibition.
对伯氨喹（PQ）脲酰胺5a - f进行了抗菌、生物膜清除和抗氧化活性筛选。受试微生物物种对受试化合物的敏感性表现出物种和化合物依赖性活性。N -（二苯甲基）- 2 - [（{4 - [（6 - 甲氧基喹啉 - 8 - 基）氨基]戊基}氨基甲酰基）氨基] - 4 - 甲基戊酰胺（5a）和2 -（4 - 氯苯基）- N -（二苯甲基）- 2 - [（{4 - [（6 - 甲氧基喹啉 - 8 - 基）氨基]戊基}氨基甲酰基）氨基]乙酰胺（5d）对金黄色葡萄球菌菌株表现出抗菌活性（MIC = 6.5 μg/ml）。此外，化合物5c和5d对大肠杆菌和铜绿假单胞菌具有较弱的抗菌活性。受试化合物均未表现出广谱抗真菌活性。相比之下，大多数化合物在针对大肠杆菌、铜绿假单胞菌和白色念珠菌的生物膜清除试验中表现出较强活性，与庆大霉素、两性霉素B或母体PQ相当，甚至更高。活性最强的化合物是5a和5b。受试化合物对近平滑念珠菌、粪肠球菌、热带念珠菌和克柔念珠菌的生物膜形成无活性。化合物5b - f显著抑制脂质过氧化（80 - 99%），而化合物5c表现出有趣的脂氧合酶抑制作用。
