Journal of Medicinal Chemistry 1992-10-30

Synthesis and antibacterial activity of a series of basic amides of teicoplanin and deglucoteicoplanin with polyamines.

A Malabarba, R Ciabatti, J Kettenring, R Scotti, G Candiani, R Pallanza, M Berti, B P Goldstein

Index: J. Med. Chem. 35(22) , 4054-60, (1992)

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Abstract

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.