STRUCTURE-ACTIVITY-RELATIONSHIPS ON THE TERMINAL D-AMINO-ACID MOIETY OF A NOVEL CEPHAMYCIN MT-141
STRUCTURE-ACTIVITY-RELATIONSHIPS ON THE TERMINAL D-AMINO-ACID MOIETY OF A NOVEL CEPHAMYCIN MT-141
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DOI：
10.7164/antibiotics.37.1403
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发表时间：
1984-01-01
影响因子：
3.3
通讯作者：
MATSUHASHI, M
中科院分区：
文献类型：
--
作者：
INOUYE, S;TSURUOKA, T;MATSUHASHI, M
D-氨基酸功能的化学修饰的效果，其代表C-7 β。研究了头霉素MT-141取代基对体外抗菌活性影响。MT-141对革兰氏阴性菌的活性高于革兰氏阳性菌。对革兰氏阴性菌有较强的溶菌活性。用低浓度的这种抗生素处理的大肠杆菌K-12菌株JE 1011的裂解之前，细胞频繁形成多个隆起。酰胺化或脱羧，从MT-141的D-氨基酸中去除酸性功能，导致对革兰氏阳性菌的活性增加，对革兰氏阴性菌的活性降低。用酰胺或脱羧物处理的细胞不形成多个隆起，而是形成单个隆起。去除碱性功能的D-氨基酸部分的N-乙酰化引起对革兰氏阳性和革兰氏阴性细菌的活性的显著下降。对E.大肠杆菌的细胞减少，用N-乙酸盐处理的细胞变成丝状。MT-141的D-氨基酸功能向L构型的转化导致对革兰氏阳性和革兰氏阴性生物的活性适度下降。对大肠杆菌具有溶菌活性和杀菌活性。大肠杆菌中的L-同源物减少。头孢西丁、头孢美唑和拉氧头孢作为参比抗生素对大肠杆菌的杀菌活性均低于MT-141。在MIC水平附近诱导细胞形成单个突起或突起。细胞表面渗透性，对β-内酰胺酶和对青霉素结合蛋白的结合亲和力。MT-141及其衍生物在大肠杆菌中的表达没有差异。
The effect of chemical modification of the D-amino acid function, which represents the C-7.beta. substituent of cephamycin MT-141 on in vitro antibacterial activity was examined. MT-141 was more active on Gram-negative organisms than Gram-positive ones. It showed strong bacteriolytic activity on Gram-negative organisms. Lysis of Escherichia coli K-12 strain JE1011 treated with a low concentration of this antibiotic was preceded by frequent formation of multiple bulges from the cells. Amidation or decarboxylation, removing the acidic function from the D-amino acid of MT-141, resulted in an increase in activity against Gram-positive bacteria, and a decrease against Gram-negative ones. Cells treated with the amide or the decarboxylate did not form multiple bulges but formed single bulges. N-Acetylation of the D-amino acid moiety removing the basic function, caused a marked drop in the activity against both Gram-positive and Gram-negative bacteria. The bacteriolytic activity on E. coli was reduced, and cells treated with the N-acetate became filamentous. Conversion of the D-amino acid function of MT-141 to the L configuration caused a moderate drop in activity against both Gram-positive and Gram-negative organisms. Both bacteriolytic and bactericidal activities against E. coli were reduced in the L-congener. Cefoxitin, cefmetazole and latamoxef used as reference antibiotics were less active than MT-141 in the bactericidal activity against E. coli, and induced single bulge formation or filamentation of the cells around MIC levels. Cell-surface permeability, stability to .beta.-lactamases, and binding affinity to PBP [penicillin binding proteins] of E. coli did not differ between MT-141 and its derivatives.