Aminoglycoside derivatives antibacterial activity

For gentamycin derivatives, the introduction of an axial hydroxymethyl substituent at C-1 in the 2-deoxystreptamine moiety reportedly ameliorates nephrotoxicity and confers protection against inactivation by bacterial enzymes. The Belgium team investigated a similar modification in the kanamycin B series [265]. As expected, l-C-(hydroxymethyl)kanamycin B (212) proved equipotent with the parent aminoglycoside (208) against kanamycin B-sensitive bacteria and the introduction of a 6"-azido, 6"-chloro, or 6"-acetamido group (213)-(215), did not reduce antibacterial activity Table 3.19). However, the introduction of a l-C-(hydroxymethyl)... 

Amino groups play an important role in antibacterial activity of aminoglycoside antibiotics. To probe this role, 3, 4 -dideoxykanamycin B (dibekacin 194) was used to prepare hexa- and heptadeoxy derivatives (5,2, 3, 4, 4",6" and 5,2, 3, 4, 2",4",6") of kanamycin A (4) and amikacin (2). The antibacterial activity data profile of these antibiotics revealed that the amino groups are essential for antibacterial activity, and that the 2"-hydroxy group and l-A-(5)-4-amino-2-hydroxybutanoyl (AHB) moiety markedly increase the activity of the antibiotic [98]. 

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]. 

A-Glysyllysinomicin (415) and several 4-A-aminoacyl analogs of lysinomicin derivatives (compounds 416 18) have been prepared to examine the effect of 4-A-aminoacylation on antibacterial activity of this class of aminoglycoside antibiotics (compounds 414 18 ). In contrast to lysinomicin, which is slightly more potent than fortimicin A (372), the new analogs showed lower activity than the 4-A-unsubstituted lysinomicin derivatives, indicating that the structure-activity relationship observed with fortimicins does not apply to lysinomicin derivatives [248]. 

Methoxy-P2 and 4 -methoxyneamine 95 are less active than neamine and inactive against resistant strains of bacteria. The 3 -deoxy derivatives show antibacterial activity against such resistant bacteria, which are known to inactivate aminoglycosides by 0-phosphorylation at the 3 -position. 

N-acylated compounds with low antibacterial activity were among the products formed when ribostamycin was acylated. A comprehensive study of the influence of HABA and its analogues on the antibacterial activity of the aminoglycosides has been published by T. H. Haskell A large number of 1-N-acylated butirosin derivatives was synthesised in the following way (Fig. 34) ... 

Dibekacin has been converted to 2"-amino-2"-deoxy-arbekacin and five analogues, some showing potent antibacterial activity. and C N.m.r. studies on aminoglycoside antibiotics have been reported, vdiich served to confirm the conformations of -demethylclindamycin and some cyclic derivatives. ... 

Three o<-glycosides (15) of 2,5,6-trideoxystreptamine have been prepared using maltal and lactal derivatives by stereospecific ex -glycosylation with a chiral ditosyloxy-cyclohexanol followed by conventional amination via azidolysis. These ex -disaccharide-2,5,6- trideoxystreptamines, analogues of aminoglycoside antibiotics, showed no antibacterial activity. Since monosaccharide 2,5,6-trideoxystreptamine analogues were active, the... 

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