amino group free or acylated with trifluoroacetyl group. The antiviral activities of these compounds were excellent and almost similar to each other, but those with trifluoroacetyl group at the 3"-amino group exhibited reduced cytotoxicity on Vero cell [133]. Likewise, N-palmitoyl derivatives of kanamycin B, tobramycin (3'-de-oxykanamycin B), dibekacin (3',4'-dideoxykanamycin B), and gentamicin (C1, C1a, and C2 complex), and a few other aminoglycosides were prepared, all of which showed excellent antiviral activity [134].

Aminoglycoside antibiotics (257), including kanamycin A, tobramycin, and gentamicin C complex, have been acylated with 1 mole of disodium carbenicillin (258) to give monoacylated derivatives (e.g., 259) (compounds 257-259). The resulting compounds were devoid of antibacterial activity against several strains tested, however, and showed no toxicity [135].

The 1-N-(D-threo- and racemic erythro-3-amino-2-hydroxylbutanoyl)-2',3'-di-deoxykanamycins A have been synthesized by using a standard esterification procedure to acylate the amino group of kanamycin A at position 1 with the corresponding 3-azido-2-hydroxybutanoic acid. The antibacterial activities of these compounds were less than that of amikacin having a 4-amino-2-hydroxybutanoyl moiety at the 1-amino group [136].

In a study on the fluorination-toxicity relationship, investigators prepared 1-N-acylamido derivatives of kanamycins, including (2R,3R)- and (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoylkanamycins A and B (compounds 262-265). The 1-N-[(2R,3R)-4-amino-3-fluoro-2-hydroxybutanoyl] derivatives 262-264 showed activity similar to that of the related compounds [amikacin (2), arbekacin (260), and 1-N-[(S)-4-amino-2-hydroxybutanoyl]-3'-deoxykanamycin B 261], whereas the (2R,3S)-derivative 265 (compounds 260-265 ) showed decreased activity relative to 260. In toxicity, these compounds were similar to the parent antibiotics, and fluorination did not show any influence in the toxicity of the antibiotics [137].

6' -N-Benzamido derivatives of kanamycin A and tobramycin having a chromium complex in the benzene ring were prepared for use as metallotracers in im-munoassay studies. To make these compounds, N-hydroxysuccinimide-activated esters of these organochromiums were treated with kanamycin A or tobramycin to selectively produce the 6'-N-acylated derivative [138].

Different amino acid and peptide derivaties were used to synthesize a series of aminoacyl and dipeptidyl derivatives of kanamycin A and netilmicin modified at the 1-, and 6'-amino groups by selective acylation of the copper complexes of these antibiotics. However, none of these modified compounds were active against either gram-positive or gram-negative bacteria [139]. Recently, in a report from Abbott

0 0

Post a comment