In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates.
In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates.
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DOI：
10.1371/journal.pone.0164227
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Seleem MN
中科院分区：
文献类型：
--
作者：
AbdelKhalek A;Ashby CR Jr;Patel BA;Talele TT;Seleem MN
细菌感染由于对许多常规抗菌药物的耐药性的出现，对医疗保健从业者提出了严重的挑战。因此，新的细菌靶点和新的抗菌剂尚未得到满足。罗丹宁衍生物通过一种新的机制被证明具有有效的抗菌活性。然而，它们作为抗菌药物的潜在用途尚未得到充分研究。在这项研究中，我们测定了7种罗丹宁衍生物（化合物Rh 1-7）对临床分离的革兰氏阳性和革兰氏阴性菌株以及白色念珠菌的活性谱。我们还合成并测试了另外三种化合物，罗丹宁2的乙酯和酰胺（分别为Rh 8和Rh 10）和罗丹宁3的乙酯（Rh 9），以确定羧基修饰对抗菌活性和人血清白蛋白结合的意义。肉汤微量稀释试验证实Rh 1-7对革兰氏阳性病原体具有杀菌活性。Rh 2对各种耐万古霉素（MIC90 = 4 μM）和耐甲氧西林（MIC90 = 4 μM）金黄色葡萄球菌（VRSA和MRSA）、表皮葡萄球菌（MIC = 4 μM）和耐万古霉素肠球菌（VRE）菌株（MIC90 = 8 μM）均有显著活性。罗丹宁化合物对芽孢杆菌（包括炭疽芽孢杆菌）具有较强的抑制活性，MIC范围为2 ~ 8 μM。此外，它们对艰难梭菌有较强的活性。最有效的化合物Rh 2在其MIC的4倍和8倍时，可显著减少表皮葡萄球菌的生物膜质量，分别超过35%和45%。罗丹宁化合物对1)革兰氏阴性病原菌（鲍曼不动杆菌、大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和鼠伤寒沙门菌）和2)白色念珠菌（MIC > 64 μM）均无抗菌活性（MIC > 128 μM）。MTS实验证实罗丹宁对64 μM的小鼠巨噬细胞（J774.1A）、32 μM的人角质形成细胞（HaCat）和128 μM的人回盲结肠直肠细胞（HRT-18）均无毒性。总的来说，这些数据表明，某些罗丹宁化合物可能具有治疗几种多重耐药革兰氏阳性细菌感染的潜在用途。
Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives have been shown to possess potent antimicrobial activity via a novel mechanism. However, their potential use as antibacterials has not been fully examined. In this study, we determined the spectrum of activity of seven rhodanine derivatives (compounds Rh 1–7) against clinical isolates of Gram-positive and Gram-negative bacterial strains and Candida albicans. We also synthesized and tested three additional compounds, ethyl ester and amide of rhodanine 2 (Rh 8 and Rh 10, respectively) and ethyl ester of rhodanine 3 (Rh 9) to determine the significance of the carboxyl group modification towards antibacterial activity and human serum albumin binding. A broth microdilution assay confirmed Rh 1–7 exhibit bactericidal activity against Gram-positive pathogens. Rh 2 had significant activity against various vancomycin-resistant (MIC90 = 4 μM) and methicillin-resistant (MIC90 = 4 μM) Staphylococcus aureus (VRSA and MRSA), Staphylococcus epidermidis (MIC = 4 μM) and vancomycin-resistant Enterococcus (VRE) strains (MIC90 = 8 μM). The rhodanine compounds exhibited potent activity against Bacillus spp., including Bacillus anthracis, with MIC range of 2–8 μM. In addition, they had potent activity against Clostridium difficile. The most potent compound, Rh 2, at 4 and 8 times its MIC, significantly decreased S. epidermidis biofilm mass by more than 35% and 45%, respectively. None of the rhodanine compounds showed antimicrobial activity (MIC > 128 μM) against various 1) Gram-negative pathogens (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella Typhimurium) or 2) strains of Candida albicans (MIC > 64 μM). The MTS assay confirmed that rhodanines were not toxic to mouse murine macrophage (J774.1A) up to 64 μM, human keratinocytes (HaCat) up to 32 μM, and human ileocecal colorectal cell (HRT-18) up to 128 μM. Overall, these data suggest that certain rhodanine compounds may have potential use for the treatment of several multidrug-resistant Gram-positive bacterial infections.
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影响因子：
3.3
作者：
Mohammad, Haroon;Mayhoub, Abdelrahman S.;Seleem, Mohamed N.
通讯作者：
Seleem, Mohamed N.
影响因子：
2.7
作者：
Patel, Bhargav A.;Ashby, Charles R., Jr.;Talele, Tanaji T.
通讯作者：
Talele, Tanaji T.
影响因子：
39.2
作者：
CHRISTENSEN, GD;BISNO, AL;LUTHER, RW
通讯作者：
LUTHER, RW
影响因子：
3.5
作者：
Patel, Bhargav A.;Krishnan, Ramalingam;Talele, Tanaji T.
通讯作者：
Talele, Tanaji T.
影响因子：
4.9
作者：
Randall, Christopher P.;Mariner, Katherine R.;O'Neill, Alex J.
通讯作者：
O'Neill, Alex J.