ANTIBACTERIAL ACTIVITY OF 15-AZASTEROIDS ALONE AND IN COMBINATION WITH ANTIBIOTICS
ANTIBACTERIAL ACTIVITY OF 15-AZASTEROIDS ALONE AND IN COMBINATION WITH ANTIBIOTICS
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DOI：
10.1016/0039-128x(76)90086-6
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发表时间：
1976-01-01
期刊：
影响因子：
2.7
通讯作者：
BERLIN, KD
中科院分区：
文献类型：
--
作者：
CHESNUT, RW;DURHAM, NN;BERLIN, KD
合成了一类新的15-氮杂甾体类似物，并测试了其抗微生物活性。化合物1，10，11，11 a-四氢-7-甲氧基-11 a-甲基-2H-萘（1，2-g）吲哚（甲氧基亚胺）和1，10，11，11 a-四氢-11 a-甲基-2H-萘（1，2-g）吲哚-7-醇（羟基亚胺）在低至10-5 M的浓度下抑制枯草芽孢杆菌和大肠杆菌的生长。向生长培养基中添加任一化合物均导致放射性葡萄糖、尿嘧啶和几种氨基酸转运的快速抑制。从培养基中去除类固醇后，生长和底物转运的抑制被逆转。这一证据与类固醇作用于细胞外围的部位一致。将甲氧亚胺与亚抑制浓度的多粘菌素或环蛋白组合，产生了极大增强的对荧光假单胞菌的抗微生物活性。对B也观察到类似的作用。当氮杂甾体与万古霉素或氯霉素组合时，其他抗生素如青霉素或红霉素的抑制作用不受加入供试化合物的影响。氮杂甾体和抗生素之间形成的分子复合物，这是负责增强生物活性的建议。
A new class of 15-azasteroid analogues was synthesized and tested for antimicrobial activity. The compounds 1,10,11,11a-tetrahydro-7-methoxy-11a-methyl-2H-naphth (1,2-g) indol (methoxyimine) and 1,10,11,11a-tetrahydro-11a-methyl-2H-naphth (1,2-g) indol-7-ol (hydroxyimine) inhibit the growth of Bacillus subtilis and Escherichia coli at concentrations as low as 10-5 M. Addition of either compound to the growth medium caused a rapid inhibition in the transport of radioactive glucose, uracil and several amino acids. The inhibition of growth and substrate transport was reversed following removal of the steroid from the medium. The evidence is consistent with a site of steroid action at the cell periphery. Combining the methoxyimine with polymyxin or circulin at subinhibitory concentrations produced greatly enhanced antimicrobial activity against Pseudomonas fluorescens. Similar action was observed against B. subtilis when the azasteroid was combined with vancomycin or chloramphenicol. The inhibitory action of other antibiotics such as penicillin or erythromycin was not affected by addition of the test compound. Formation of a molecular complex between the azasteroid and antibiotic which is responsible for the enhanced biological activity is suggested.