1 research outputs found
Synthesis and Antiribosomal Activities of 4ā²ā<i>O</i>ā, 6ā²ā<i>O</i>ā, 4ā³ā<i>O</i>ā, 4ā²,6ā²ā<i>O</i>- and 4ā³,6ā³ā<i>O</i>-Derivatives in the Kanamycin Series Indicate Differing Target Selectivity Patterns between the 4,5- and 4,6-Series of Disubstituted 2āDeoxystreptamine Aminoglycoside Antibiotics
Chemistry
for the efficient modification of the kanamycin class of 4,6-aminoglycosides
at the 4ā²-position is presented. In all kanamycins but kanamycin
B, 4ā²-<i>O</i>-alkylation is strongly detrimental
to antiribosomal and antibacterial activity. Ethylation of kanamycin
B at the 4ā³-position entails little loss of antiribosomal and
antibacterial activity, but no increase of ribosomal selectivity.
These results are contrasted with those for the 4,5-aminoglycosides,
where 4ā²-<i>O</i>-alkylation of paromomycin causes
only a minimal loss of activity but results in a significant increase
in selectivity with a concomitant loss of ototoxicity