Antibacterial Properties of Some Cyclic Organobismuth(III) Compounds
Antibacterial Properties of Some Cyclic Organobismuth(III) Compounds
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DOI：
10.1128/aac.49.7.2729-2734.2005
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发表时间：
2005-07
影响因子：
4.9
通讯作者：
T. Kotani;Daisuke Nagai;Kensuke Asahi;Hitomi Suzuki;F. Yamao;N. Kataoka;T. Yagura
中科院分区：
文献类型：
--
作者：
T. Kotani;Daisuke Nagai;Kensuke Asahi;Hitomi Suzuki;F. Yamao;N. Kataoka;T. Yagura
铋化合物因其在哺乳动物中的低毒性水平而为人所知，并且各种类型的铋盐已被用于治疗医学病症。作为我们的计划的一部分，以探测这方面的铋化学，环状有机铋化合物1至8轴承的氮或硫原子作为一个额外的环成员已被合成，并对革兰氏阴性和革兰氏阳性细菌的五个标准菌株的抗微生物活性进行了评估。八元环化合物，化合物1至3，表现出对金黄色葡萄球菌的MIC小于0.5 μ g/ml，并且比六元环化合物，化合物5至8（MIC，4.0至16 μ g/ml）更有活性。革兰氏阳性菌（金黄色葡萄球菌，枯草芽孢杆菌，粪肠球菌）更容易受到这两种类型的环化合物比革兰氏阴性菌（大肠杆菌和铜绿假单胞菌）。用多粘菌素B九肽处理可增加E.大肠杆菌的环状有机铋化合物，表明革兰氏阴性菌的外膜的化合物的低渗透性。化合物1对耐甲氧西林沙门氏菌也有一定的抑制作用。金黄色葡萄球菌，其对90%的医院储备菌株的MIC为1.25 μ g/ml。S.用化合物1或3处理的金黄色葡萄球菌在低剂量（2 × MIC）下显示出静态效应。然而，当S.用10 × MIC的化合物1或3处理金黄色葡萄球菌，在处理48小时后，活细胞数减少约3-log。电子显微镜检查表明，S的大小有相当大的增加。金黄色葡萄球菌和在用0.5 × MIC的化合物1处理后经历细胞分裂的细胞的比例。
ABSTRACT Bismuth compounds are known for their low levels of toxicity in mammals, and various types of bismuth salts have been used to treat medical disorders. As part of our program to probe this aspect of bismuth chemistry, cyclic organobismuth compounds 1 to 8 bearing a nitrogen or sulfur atom as an additional ring member have been synthesized, and their antimicrobial activities against five standard strains of gram-negative and gram-positive bacteria were assessed. The eight-membered-ring compounds, compounds 1 to 3, exhibited MICs of less than 0.5 μg/ml against Staphylococcus aureus and were more active than the six-membered ones, compounds 5 to 8 (MICs, 4.0 to 16 μg/ml). The gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis) were more susceptible to both types of ring compounds than the gram-negative ones (Escherichia coli and Pseudomonas aeruginosa). Treatment with polymyxin B nonapeptide increased the susceptibility of E. coli to cyclic organobismuth compounds, indicating the low permeability of the outer membrane of gram-negative bacteria to the compounds. Compound 1 also had activity against methicillin-resistant S. aureus, which had an MIC for 90% of the hospital stock strains of 1.25 μg/ml. The killing curves for S. aureus treated with compound 1 or 3 revealed a static effect at a low dose (2× the MIC). However, when S. aureus was treated with 10× the MIC of compound 1 or 3, there was an approximately 3-log reduction in the viable cell number after 48 h of treatment. Electron microscopic inspection demonstrated a considerable increase in the size of S. aureus and the proportion of cells undergoing cell division after treatment with compound 1 at 0.5× the MIC.