Malabarba A, Ciabatti R, Kettenring J, Scotti R, Candiani G, Pallanza R, Berti M, Goldstein B P
Marion Merrell Dow Research Institute, Lepetit Research Center, Gerenzano (Varese), Italy.
J Med Chem. 1992 Oct 30;35(22):4054-60. doi: 10.1021/jm00100a010.
Basic carboxamides of teicoplanin A2 (CTA) and its aglycon (TD) are prepared by condensation of the 63-carboxyl function of these antibiotics with linear or branched polyamines. The antimicrobial activities of some of the resulting compounds were better than those of the unmodified antibiotics. The presence of more than one basic group in the amidic chain enhanced the in vitro activity of some TD-amides against Gram-negative bacteria; two of these derivatives were also effective in vivo against Escherichia coli septicemia in the mouse. Among the CTA derivatives, the amide with spermine showed some unexpected in vitro activity against Gram-negatives. Both CTA- and TD-amides with polyamines are very soluble in water over a wide range of pH and are very hydrophilic.
替考拉宁A2（CTA）及其苷元（TD）的碱性羧酰胺是通过这些抗生素的63-羧基官能团与直链或支链多胺缩合制备的。一些所得化合物的抗菌活性优于未修饰的抗生素。酰胺链中存在多个碱性基团增强了一些TD-酰胺对革兰氏阴性菌的体外活性；其中两种衍生物在体内对小鼠大肠杆菌败血症也有效。在CTA衍生物中，与精胺形成的酰胺对革兰氏阴性菌表现出一些意外的体外活性。CTA-和TD-与多胺形成的酰胺在很宽的pH范围内都非常易溶于水，且具有很强的亲水性。
