Duchenko К. А., Kornienko V. І., Ladogubets Е. V., Ponomarenko О. V., Harkusha І. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Purpose. To study the acute toxicity and dependence of anti-inflammatory activity from chemical structures in a series of 8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide derivatives. Object and methods of the research. The object of the study are 8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide derivatives. The study of acute toxicity of 8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide derivatives was held on intact white non-linear mice. LD50 was calculated by Karber’s method. Experimental evaluation of the anti-inflammatory activity of 8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide derivatives was done on acute inflammatory carrageen paw edema in rats caused by subplantar injection of 1% solution. Maximum anti-inflammatory activity of bioactive substances revealed while acute inflammatory edema, which is accompanied by a pronounced exudation. Sodium diclofenac served as the reference drug. Digital data processing was carried out by the method of variative statistics using one-way ANOVA test on the Originpro 7.5 software. Results and discussion. It was found that the LD50 is in 650 to 940 mg/kg range. In accordance with Sidorov’s classification, all 5 compounds are related to moderately toxic substances among investigated derivatives of 8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide. The results of experimental research of anti-inflammatory activity for the first synthesized 8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide derivatives suggest, that the most pronounced antiexudative effect has compound № 1 – 5-nitrofuryl-2-propenylidenehydrazide-8-morpholinotheophyllinyl-7-acetic acid, which is in a dose of 32.5 mg/kg after 4 hours after administration caused a decrease in the experimental edema on 48.7%. The substitution of the 5-nitrofuryl-2-propenylidenehydrazide radical in the second position of the molecule of 8-morpholinotheophyllinyl-7-acetic acid with idolon-2-ylidene-3-hydrazide radical leads to a decrease in anti-exudative activity. Less pronounced anti-exudative activity (7.1%) has a compound that contains 5-bromoindolon-2-ylidene-3hydrazide substituent in position 7 of 8-morpholinotheophyllinyl-7-acetic acid derivative molecule. It is possible to suggest, that the anti-inflammatory effect of new synthesized derivatives of 8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide is realized by the decreasing of the release of inflammation mediators of mastocytes and inhibition of gene expression, responsible for the synthesis of inflammatory cytokines. Thus, among the investigated derivatives of 8-morpholinotheophyllinyl-7-acetic acid, the compound 1 was discovered, which helps to reduce the experimental carrageen paw edema in rats and which anti-inflammatory effect is comparable with that for the reference drug – sodium diclofenac.

8-morpholinotheophyllinyl-7-acetic acid ylidene hydrazide, acute toxicity and anti-exudative activity

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«Bulletin of problems biology and medicine» Issue 1 Part 1 (148), 2019 year, 117-120 pages, index UDK 615.324:547.857.4

10.29254/2077-4214-2019-1-1-148-117-120