Antibacterial, antifungal and antileishmanial activities of indolone-N-oxide derivatives
Antibacterial, antifungal and antileishmanial activities of indolone-N-oxide derivatives
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DOI：
10.1038/ja.2012.60
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发表时间：
2012-10-01
影响因子：
3.3
通讯作者：
Nepveu, Francoise
中科院分区：
文献类型：
--
作者：
Ibrahim, Hany;Furiga, Aurelie;Nepveu, Francoise
微生物对传统药物和经典药效团的耐药性令人担忧地增加，这刺激了对新的抗微生物化合物的研究。吲哚酮-N-氧化物（INODs）具有氧化还原药效团，最近建立了有前途的抗疟疾活性。在这项研究中，一系列的INOD的抗感染性能进行了研究。对5种革兰氏阳性（金黄色葡萄球菌、肠球菌）、革兰氏阴性（铜绿假单胞菌、大肠杆菌）和抗酸（结核分枝杆菌）菌株进行了抗菌活性评价。使用两种真菌菌株（尼日尔曲霉，白色念珠菌）的抗真菌活性进行评估。针对两种利什曼原虫菌株、无菌培养的无鞭毛体（婴儿利什曼原虫、亚马逊利什曼原虫）测试抗利什曼原虫活性。的药理活性进行了讨论，作为一个功能的结构和亲脂性特征。革兰氏阳性菌E.结果表明，耐药菌株中以大肠杆菌最敏感，而革兰氏阴性E.大肠杆菌对这类化合物具有抗性。一个化合物（64）对E.另一株（52株）与克霉唑对C.白色念珠菌。INOD是杀微生物的，而不是静态的。INOD在低微摩尔范围内显示出良好的抗结核活性（与环丙沙星相似）。此外，还证实了INOD-抗原虫对利什曼原虫的效力。INOD显示出广谱的抗菌活性，并提供了一个有前途的抗感染原型值得开发。The Journal of Antibiotics（2012）65，499-504; doi：10.1038/ja.2012.60; 2012年7月25日在线发表
An alarming increase in microbial resistance to traditional drugs and classical pharmacophores has spurred the search for new antimicrobial compounds. Indolone-N-oxides (INODs) possess a redox pharmacophore with promising, recently established, antimalarial activities. In this study, the anti-infectious properties of a series of INODs were investigated. The antibacterial activity was evaluated against five bacterial strains Gram-positive (Staphylococcus aureus, Enterococcus hirae), Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and acid-fast (Mycobacterium tuberculosis). The antifungal activity was assessed using two fungal strains (Aspergillus niger, Candida albicans). The antileishmanial activity was tested against two leishmanial strains, axenically-cultured amastigote (Leishmania infantum, Leishmania amazonensis). The pharmacological activities are discussed as a function of structural and lipophilic characteristics. The Gram-positive bacterial strain E. hirae was found to be the most sensitive strain, whereas the Gram-negative E. coli was resistant to this family of compounds. One compound (64) was more potent than nalidixic acid against E. hirae, whereas another one (52) was equipotent as clotrimazole against C. albicans. INODs were microbe -cidal rather than -static. INODs showed good antitubercular activity in the low micromolar range (similar to ciprofloxacin). In addition, INOD-antiprotozoal potencies were confirmed against the leishmania parasite. INODs showed a broad spectrum of antimicrobial activity and offer a promising anti-infectious prototype worthy of being developed. The Journal of Antibiotics (2012) 65, 499-504; doi:10.1038/ja.2012.60; published online 25 July 2012