Cytostatic agents. 9. Relations between physicochemical properties and antimicrobial activity of beta -amino ketones

Abstract

The relation between antibacterial and antifungal activities of 6 aliphatic beta -amino ketones, 5 alpha -phenyl-beta -amino ketones, 8 beta -amino propiophenones, and 9 alpha -phenyl-beta -amino propiophenones and partition coeff., H2O soly. of the base, and total soly. was studied. The bacteriostatic effect of all investigated beta -amino ketones was small, but the fungistatic effect, with the exception of aliphatic compds., was good. Aliphatic beta -amino ketones of lower mol. size, 1-dimethylamino-2-isopropylpropan-3-one, 1-dimethylamino-2-isobutylpropan-3-one, and 1-dimethylamino-2,3-dimethylpropan-3-one, showed good H2O soly. and a partition coeff. <0.1 but had weak antifungal activity. Increasing the length of the alkyl residue, as in 1-dimethylamino-2-hexyl-3-methylpropan-3-one and 1-dimethylamino-2-octyl-3-methylpropan-3-one, increased lipid soly. but reduced antifungal activity. Of the alpha -phenyl-beta -amino ketones, 1-dimethylamino-2-phenylbutan-3-one and 1-pyrrolidinyl-2-phenylbutan-3-one had the greatest H2O soly. and their partition coeff. was <0.4; both compds. had good antifungal activity. Increasing lipid soly. did not increase antifungal properties. 1-Diethylamino-2-phenylbutan-3-one had the greatest fungistatic activity. Also in the beta -amino propiophenone series no relation between the phys.-ch em. properties and fungistatic activity was noted. Good lipid sol. compds., such as 1-piperidino-3-p-propoxyphenylpropan-3-on e and 1-dimethylamino-2-dimethyl-3-phenylpropan-3-one, had the least activity, while hydrophilic compds., such as 1-dimethylamino-2-methyl-3-phenylpropan-3-one, were quite effective. All of the alpha -phenyl-beta -amino propiophenones, with the exception of 1-dimethylamino-2-(3-methoxyphenyl)-3-(3-methoxyphenyl)propan-3-one, showed good to very good fungistatic effects independent of their phys.-chem. properties; 1-dimethylamino-2-phenyl-3-phenylpropan-3-one, 1-dimethylamino-2-(4-chlorophenyl)-3-phenylpropan-3-one, and 1-piperidino-2-phenyl-3-phenylpropan-3-one were the most active. Chelation with Cu2+ or Fe3+ was excluded as the mechanism of action of beta -amino ketones.