Dudikova D. Antimicrobial properties of 1-[4-(1-adamantyl)-phenoxy]-3-dialkylamino-2-propanol quaternarysalts. – Qualifying scientific work on the rights

In the thesis, it provides a new solution of the challenging issue of pharmacology. The prospects for the quaternary salts of 1-[4-(1-adamantyl)-phenoxy]-3-dialkylamino-2-propanol development as new antimicrobial drugs were evaluated using microbiological, pharmacological, biochemical, electron microscopic and physic-chemical methods of research. The advisability of developing effective and safe antimicrobial agents on their basis was confirmed by the results of the study of the activity spectrum, mechanism of action, toxicity and in vivo efficacy. The reported results showed that the quaternary salts of 1- [4- (1-adamantyl)-phenoxy]-3-dialkylamino-2-propanol possess a broad spectrum of antimicrobial activity, which is ensured by the presence 4-(1-adamantyl)-phenyl radical. Activity against P. aeruginosa was revealed in the presence the benzyl radical with either dimethylamine or saturated 5-membered and 6-membered heterocycles (pyrrolidine and morpholine respectively). Selected in screening studies, compounds of UK-23 and KVM-97 possess inhibitory effects on both planktonic microorganisms and biofilms. In vitro studies have shown that the compounds possess bactericidal and fungicidal effects; their activity is independent of pH and decreases with increasing of inoculum. KVM-97 was also effective in rabbit staphylococcal conjunctivitis model. Under the treatment with KVM-97 (0.025 % solution) a strainof S. aureus in eyes conjunctival fluid was not detected on the first day, the complete disappearance of the disease symptoms was recorded for the fourth day; in the control animals - after the twelfth day. The efficacy of compound KVM-97 in staphylococcal conjunctivitis model is comparable to the 0.3% solution of tobramycin and superior that of a 30.0% solution of sodium sulfacyl.