Olesya Aksenovska

New hydroxyl-functionalized aromatic sulfonamide, N-butyl-4-(3-hydroxypropylamino)benzenesulfonamide (BHPA-BSA), has been synthesized and tested as potential plasticizer for polyamide 12 (PA-12). According to results of quantum-chemical calculations, BHPA-BSA has a higher binding energy with the monomer unit of PA-12 compared to commercial plasticizers N-butylbenzenesulfonamide (BBSA) and N-(3-hydroxypropyl)benzenesulfonamide (HP-BSA). Specific combination of the sulfonamide and hydroxyalkyl groups in BHPA-BSA allows the formation of two hydrogen bonds with the amide group of PA-12 through one of the sulfonamide’s oxygen atom as a hydrogen bond acceptor and hydroxyl group as a hydrogen bond donor. PA-12 films containing 15 and 20 wt% BHPA-BSA or commercial plasticizers have been prepared by compression moulding. IR analysis revealed that both sulfonamide and hydroxyl groups of BHPA-BSA participate in the hydrogen bonding with the amide group of PA-12. Differential scanning calorimetry show that the new sulfonamide lowers the glass transition temperature of PA-12 by more than 40 °C, indicating a plasticizing effect comparable to common plasticizers. The results of dynamic mechanical analysis also revealed the high plasticizing efficacy of BHPA-BSA toward PA-12, which is manifested in the twofold reduction in the storage modulus of the polymer.The volatility of the BHPA-BSA from the PA-12 matrix at 120 °C is five times lower than that of commercial plasticizers. Moreover, the new sulfonamide exhibits excellent resistance to release in hexane, in contrast to BBSA and HP-BSA. Thus, the functionalization of BBSA with the hydroxyalkyl group is an efficient approach to synthesize new low-volatility plasticizers for polyamide resins.

Синтезовано довголанцюговий біологічно активний естер 4-гідроксибензойної кислоти – додецил-4-гідроксибензоат (ДГБ). Отримано композиційні полімерні плівки на основі поліаміду 12 (ПА-12), які містять 25 масових відсотків ДГБ. Методом диференційної сканувальної калориметрії встановлено, що ДГБ знижує температуру склування ПА-12 від 46 до -25 °С і температуру плавлення від 178 до 168 °С. Це свідчить про високу ефективність сполуки як пластифікатора для ПА-12. Згідно з результатами термогравіметричного аналізу, полімерна композиція ПА-12/ДГБ має температуру початку деструкції 324 °С і є термічно стійкою в області температур промислової переробки ПА-12 (220-300 °С). ДГБ є перспективною поліфункціональною модифікуючою домішкою до поліамідів технічного і медичного призначення, яка може суттєво підвищувати гнучність полімерних виробів і надавати їм антимікробних властивостей.

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 (Trans-CNF), 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 C. albicans ATCC 10231, C. albicans, C. glabrata and C. 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 C. albicans, C. glabrata, and C. 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 14a-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.

Cationic polymer polyhexamethylene guanidine hydrochloride (PHMG-Cl) is promising biocide that combines a broad spectrum of antimicrobial activity, mod-erate toxicity, as well as reasonable cost. It is widely used as an effective disinfect-ant in cooling systems, swimming pools, and hospitals, personal hygiene products, etc. Recently PHMG-Cl was found to have pronounced anti-inflammatory and wound healing properties and therefore may be used for the treatment of chronic wounds and thermal burns. This may indicate the antioxidant activity of polymeric biocide. In this study, PHMG-Cl has been synthesized by melt polycondensation of guanidine hydrochloride and 1,6-hexamethylenediamine. The structure of the cati-onic polymer was confirmed by 1H NMR and IR spectroscopy. The viscosity-average molecular weight of PHMG-Cl was found to be 10700. The antioxidant activity of PHMG-Cl has been studied by using different methods. In the methylene blue (MB) dye test, the oxidation of MB by hydroxyl radicals generating in Fenton’s system was found to decrease in the presence of PHMG-Cl in a molar ratio to MB of 5:1 and 10:1 (by 26 % and 38 %, respectively). At the same time, complete dye oxidation was observed when guanidine hydrochloride was used instead of PHMG-Cl. The antioxidant activity of PHMG-Cl has also been studied in the model system of radical chain oxidation of benzyl alcohol (BA). In this system, alkyl and peroxyl radicals are formed. The antioxidant activity was determined by a decrease of the initial rate of oxygen absorption during the initiated oxidation of BA. The introduc-tion of PHMG-Cl into the oxidized system in the concentrations ranged from 1.3·10-3 - 1.6·10-2 mol/l decreased the oxidation rate of BA by 4.5–88 %. This result demonstrates that PHMG-Cl effectively inhibits radical chain oxidation of BA. However, further research is needed to elucidate the mechanism of free radical de-activation by a polymer biocide.