Action mechanism of antimicrobial beta -amino ketones

Abstract

Structure-activity relations of aliphatic beta -aminoketones, beta -aminopropiophenones, alpha -phenyl-beta -aminoketones, and alpha -phenyl-beta -aminopropiophenones against fungis, yeasts, and gram-pos., and gram-neg. bacteria showed that the fungicidal activity was due to the beta -amino ketone structure. Substitution of a Ph group on either the alpha -C or carbonyl C increased fungicidal activity, whereas substituents on either the amino group or the benzene ring had no effect. No correlations were found between the phys.-chem properties of these compds. and their resp. activity as fungicides. Addn. of Cu2+ to the beta -aminoketones did not alter their antimicrobial properties. The action of beta -aminoketones as fungicides depended on formation of active breakdown products, H2CO and alpha ,beta -unsatd. ketones; a rapid rate of breakdown indicated increased fungicidal activity. 1-Dimethylamino-2-methyl-3-phenyl-3-propanone decreased the wt. of Yoshida-sarcoma or sarcoma 180 by 40%; generally, beta -aminoketones inhibited tumor growth of sarcoma 180 in mice by 50%; aliphatic beta -aminoketones had no tumor inhibiting properties. The tumor inhibiting properties of aromatic beta -aminoketones depended on the acetylation and aminomethylation of biol. cell substituents such as enzymes, DNA, or RNA.