Discovery, chemistry, and activity of amikacin.
Elucidation of the mechanism of R-factor-mediated resistance to aminoglycoside antibiotics was a noteworthy scientific achievement that led to the search for and design of new structural modifications of aminoglycosides that would render them resistant to inactivation by bacterial enzymes and increase their activity against resistant organisms. Amikacin is a derivative of kanamycin A, obtained through acetylation with the L(-)-gamma-amino-alpha-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety. Its antibacterial activity is generally equal to or greater than that of kanamycin against sensitive organisms, and it is also active against aminoglycoside-resistant strains of various species. The special significance of the site of acylation and the configuration of the acid side chain were established by obtaining all possible positional and configurational isomers. Studies of a series of amikacin analogs indicated that the alpha-hydroxyl group and the terminal basic function in the side chain both play a very important role in the antimicrobial activity of amikacin.
D000583:Amikacin / Q000031:analogs & derivatives / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004755:Enterobacteriaceae / Q000187:drug effects; D007612:Kanamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects
D007612:Kanamycin; D000583:Amikacin