Synthesis and biological activity of some amide derivatives of the lantibiotic actagardine.
A series of basic carboxamides of actagardine (1), a lantibiotic possessing good antistreptococcal activity, were synthetized. Some physico-chemical characteristics, in particular charge and lipophilicity, that influence water solubility were determined. The in vitro and in vivo activity was evaluated. The monocarboxamides were generally more active than actagardine against selected Gram-positive bacteria. The 3,3-dimethylamino-1-propylamide hydrochloride (4) showed good water solubility, bactericidal action and favourable antibacterial activity and it appears to be a suitable drug for further investigation.
Merrell Dow Research Institute, Lepetit Research Center, Varese, Italy.
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A
Malabarba
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Pallanza
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M
Berti
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B
Cavalleri
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001430:Bacteriocins; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013290:Streptococcal Infections / Q000188:drug therapy; D013291:Streptococcus / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
D000577:Amides; D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; C012993:gardimycin