ΠΠ΅ΡΠ΅Π³Π»ΡΠ΄ Π·Π° ΠΠ²ΡΠΎΡ "Rogalsky, S."
ΠΠ°ΡΠ°Π· ΠΏΠΎΠΊΠ°Π·ΡΡΠΌΠΎ 1 - 2 Π· 2
Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡΠ² Π½Π° ΡΡΠΎΡΡΠ½ΡΡ
ΠΠ°Π»Π°ΡΡΡΠ²Π°Π½Π½Ρ ΡΠΎΡΡΡΠ²Π°Π½Π½Ρ
ΠΠΎΠΊΡΠΌΠ΅Π½Ρ ΠΡΠ΄ΠΊΡΠΈΡΠΈΠΉ Π΄ΠΎΡΡΡΠΏ Antibacterial activity of 1-dodecylpyridinium tetrafluoroborate and its inclusion complex with sulfobutyl ether-B-cyclodextrin against mdr acinetobacter baumannii strains(Igor Sikorsky Kyiv Polytechnic Institute, 2023) Rogalsky, S.; Hodyna, D.; Semenyuta, I.; Frasinyuk, M.; Tarasyuk, O.; Riabov, S.; Kobrina, L.; Tetko, I.; Metelytsia, L.Background.The bacterial pathogen Acinetobacter baumanniiis one of the most dangerous multi-drug-resistant (MDR) microorganisms, which causes numerous bacterial infections. Nowadays, there is an urgent need for new broad-spectrum antibacterial agents with specific molecular mechanisms of action. Long-chain 1-alkylpyridinium salts are efficient cationic biocides which can inhibit enzymes involved in the biosynthesis of bacterial fatty acids.Incorporating these compounds into inclusion complexes with cyclic oligosaccharide B-cyclodextrin can reduce their relatively high acute toxicity.Objective. The aim of this research was to develop new anti-A.baumanniiagents based on hydrophobic 1-alkylpyridinium salt and its inclusion complex with sulfobutyl ether B-cyclodextrin (SBECD). Methods. Hydrophobiccationic biocide 1-dodecylpyridinium tetrafluoroborate (PyrC12-BF4) and its inclu-sion complex with SBECD have been synthesized. The structure of the SBECD/PyrC12-BF4complex was characterized by 1H Nuclear Magnetic Resonance spectroscopy, as well as UV spectroscopy. In vitroanti-bacterial activity of the synthesized compounds was estimated against MDR clinical isolates of A. baumanniiusing standard disc diffusion method. Acute toxicity studies were performed on Daphnia magnamodel hydro-biont.Molecular docking was performed using the crystal structure of the A.baumannii3-oxoacyl-[acyl-carrier-protein] reductase(FabG).ΠΠΎΠΊΡΠΌΠ΅Π½Ρ ΠΡΠ΄ΠΊΡΠΈΡΠΈΠΉ Π΄ΠΎΡΡΡΠΏ Antifungal activity and cytotoxicity of imidazole- and morpholine-based lysosomotropic detergents(Igor Sikorsky Kyiv Polytechnic Institute, 2025) Hodyna, D.; Kovalishyn, V.; Shulha, Yu.; Trokhimenko, O.; Aksenovska, O.; Rogalsky, S.; Metelytsia, L.Background. The spread of infectious diseases caused by drug-resistant bacteria and fungi, especially nosocomial strains, is currently considered a serious medical problem. It is known that the fungus Candida albicans is the most common causative agent of candidal infection, including the severe type. The emergence and rapid formation of drug resistance, as a risk factor in the treatment of oncological diseases burdened by candidal infection, requires new therapeutic approaches, including the study of synthetic bioregulators with antifungal and anticancer efficacy. Objective. To synthesize and to determine the antifungal activity and cytotoxicity of imidazole- and morpholine-based lysosomotropic detergents (LDs) comprising both dodecyl radicals and ester-functionalized long alkyl chains. Methods. To develop the QSAR models by the OCHEM platform, machine learning methods such as Transformer Convolutional Neural Network (Trans-CNN), Transformer Convolutional Neural Fingerprint (TransCNF), and Random Forest (RF) were used. Imidazole- and morpholine-based lysosomotropic detergents comprising both dodecyl radicals and ester-functionalized long alkyl chains were synthesized and characterized by 1H Nuclear Magnetic Resonance spectroscopy. The antifungal properties of studied compounds were estimated by the disc diffusion method against the Π‘. albicans ATCC 10231, Π‘. albicans, Π‘. glΠ°brata and Π‘. krusei clinical isolates. The in vitro cytotoxic activity of LDs was evaluated by IC50 value against the throat cancer HEp-2 cell lines. AutoDock Vina software was used for the evaluation of the synthesis compounds as ligands of several antifungal targets. Results. The identified and synthesized imidazole- and morpholine-based LDs showed high antifungal potential against all Candida spp., specifically against the fluconazole-resistant Π‘. albicans, Π‘. glΠ°brata, and Π‘. krusei clinical isolates. Imidazole-based LD 1 (IM-C12) and morpholine-based LD 4 (Mor-C12) were the most active against tested fungal strains. Molecular docking results suggest that the antifungal mechanisms of the compounds may be related to the inhibition of fungal lanosterol 14ο‘-demethylase. The cytotoxic results of the synthesized compounds against the HEp-2 cell line demonstrated that morpholine-based LDs are less cytotoxic compared to imidazole-based. Conclusions. It was found that LD IM-C12 (1) is the most promising cytostatic and antifungal agent based on the obtained results. LDs IM-CH2COOC10 (2) and Mor-C12 (4), which, under conditions of chemical modification, including through the carbon chain, may also be interesting for developing potential anticancer agents.