Молекулярний дизайн біологічно активних похідних N-фенілантранілової кислоти за моделлю de nova

• Date: 2018
• Main Authors: Svechnikova, O. M., Kolisnyk, S. V., Vinnyk, O. F., Kostina, T. A., Zhukova, T. V.
• Format: Article
• Language: Ukrainian
• Published: National University of Pharmacy 2018
• Subjects: заміщені N-фенілантранілової кислоти; протизапальна активність; молекулярний дизайн; УДК 547.835
• Online Access: https://ophcj.nuph.edu.ua/article/view/ophcj.18.937
• Journal Title: Journal of Organic and Pharmaceutical Chemistry

Most QSAR methods are based on determination of dependence of different types of biological activity of compounds on their physicochemical parameters, which determination is experimentally quite difficult, while those compounds that are calculated theoretically often have systematic deviations.Aim. To determine the increments of substituents in isostructural series of hydrazides and thiosemicarbazides of substituted N-phenylanthranilic acids for their anti-inflammatory activity by the empirical method on the de nova model.Results and discussion. The study was conducted for 18 thiosemicarbazide (batch 1) and 15 hydrazides (batch 2) of substituted N-phenylanthranilic acid. The increments calculated show that introduction of substituents in the anthranilic moiety of the thiosemicarbazide molecule increases the anti-inflammatory activity. The increments of substituents in the non-anthranilic fragment of the molecule have different signs and values, depending on the nature and position of the radical. Introduction of substituents (Cl-, NO2-) into the para-position of the anthranilic fragment of the molecule of N-phenylantranilic acid hydrazide increases the anti-inflammatory activity, while introduction of various substituents into the non-anthranilic fragment of the molecule causes both an increase and a decrease in lg P.Experimental part. The study of the anti-inflammatory activity was performed on the “formalin edema” model in rats using the oncometric method. The substances were administered orally in the form of a fine suspension stabilized by the emulsifier Tween-80 in the doses of 50 mg/kg of the animal body weight. The reference drug indomethacin was administered in the dose of 50 mg/kg.Conclusions. The increments of substituents in isostructural series of hydrazides and thiosemicarbazides of substituted N-phenylanthranilic acids have been determined by the empirical method. The dependence of the increments on the nature and position of substituents in molecules has been analyzed.