Syntheses and antimicrobial activities of alkyl lysophospholipids.
Syntheses and antimicrobial activities of alkyl lysophospholipids.
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DOI：
10.1248/cpb.30.3260
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发表时间：
1982-09
影响因子：
1.7
通讯作者：
S. Tsushima;Y. Yoshioka;S. Tanida;H. Nomura;S. Nojima;M. Hozumi
中科院分区：
文献类型：
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作者：
S. Tsushima;Y. Yoshioka;S. Tanida;H. Nomura;S. Nojima;M. Hozumi
合成了27个溶血磷脂的烷基类似物，并对其结构与抗菌活性关系进行了研究。这些类似物的不同之处在于1位的长链烷基部分和3位的β-N-取代的氨基乙基磷酰基部分的结构，以及甘油部分的2-甲氧基的存在或不存在。发现许多烷基溶血磷脂具有比天然存在的溶血素和卵磷脂对梨形四膜虫W和多种真菌（包括人类病原体）更有效的抗微生物活性。用2-甲基-1-十四烷基甘油-3-磷酸胆碱观察到最大活性。具有较长和较短烷基链的1-烷基-2-甲基甘油-3-磷酸胆碱倾向于具有较低的抗菌活性。烷基溶血磷脂与吡啶基乙基，而不是胆碱基团表现出强大的抗真菌活性与烷基甘油磷胆碱与相应的烷基，但较低的抗原虫活性。这两类化合物中的十四烷基同系物对毛癣菌属物种显示出与克霉唑相当的有效抑制活性。相比之下，烷基溶血磷脂与乙醇胺部分的极性头基团显示活性降低。将分子骨架由甘油变为1，3-丙二醇对活性影响不大，所得1-烷基-2-脱氧甘油-3-磷酸胆碱显示出与1-烷基-2-甲基甘油-3-磷酸胆碱相似的抗菌性能。
Twenty-seven alkyl analogs of lysophospholipid were synthesized and their structureantimicrobial activity relationships were examined. These analogs differed in the structures of the long-chain alkyl moiety at position 1 and the β-N-substituted aminoethylphosphoryl moiety at position 3, and in the presence or absence of the 2-methoxy group of the glycerol moiety. Many of the alkyl lysophospholipids were found to possess antimicrobial activities much more potent than those of naturally occuring lysolecithin and lecithin against Tetrahymena pyriformis W and a variety of fungi, including human pathogens. The maximal activity was observed with 2-methyl-1-tetradecylglycero-3-phosphocholines. 1-Alkyl-2-methylglycero-3-phosphocholines with longer as well as shorter alkyl chains tended to have lower antimicrobial activity. Alkyl lysophospholipids with pyridinioethyl instead of the choline group showed potent antifungal activity comparable to alkyl glycerophosphocholines with the corresponding alkyl group but lower antiprotozoal activity. The tetradecyl congeners in these two classes of compounds showed potent inhibitory activity against Trichophyton species, comparable to that of clotrimazole. In contrast, alkyl lysophospholipids with an ethanolamine moiety in the polar head group showed decreased activity. Changing the molecular backbone from glycerol to 1, 3-propanediol had little effect upon the activity, and the resulting 1-alkyl-2-deoxyglycero-3-phosphocholines displayed antimicrobial properties similar to those of 1-alkyl-2-methylglycero-3-phosphocholines.