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Evaluation of analgesic and anti-inflammatory activities of a new isoindoline-1,3-dione derivative


Yu.A. Trukhanova, D.A. Kolesnik, E.V. Kuvaeva, E.N. Kirillova, D.Yu. Ivkin
St. Petersburg State Chemical and Pharmaceutical University (SPCPU), st. prof. Popova, 14, St. Petersburg, 197376, Russian Federation

Introduction. Derivatives of isoindoline-1,3-dione make up a large group of biologically active substances with a wide spectrum of action. The N-substituted phthalimide fragment is present in the structure of many drugs (thalidomide, talmethoprim, etc.). Therefore, it is relevant to obtain previously undescribed derivatives of isoindoline-1,3-dione, as well as to evaluate their pharmacological potential. Previously, the authors obtained new N-substituted derivatives of isoindoline-1,3-dione. This article presents the results of a study of the biological activity of these compounds. Objective: The aim of the study was to determine the acute toxicity of synthesized substances of a number of N-substituted derivatives of isoindoline-1,3-dione, evaluation of the biological activity in silico and in vivo for the least toxic compound. Material and methods. Computer screening of biological activity was carried out using the PASS-online program. Prediction of acute toxicity – using the local version of the GUSAR software. For experimental evaluation of analgesic activity, the model "acetic acid cramps" was used when using sodium metamizole as a comparison drug, two models were included in the study of anti-inflammatory activity: "formalin edema of mouse paws" and "cotton granuloma in rats" when used as a comparison drug – diclofenac. Results. As a result of screening of biological activity data on the presumed analgesic activity were obtained. The initial dosages for the study of acute toxicity in vivo were determined using the GUSAR software. According to the results of the assessment of acute toxicity in vivo, the least toxic compound was found from a number of N-substituted derivatives of isoindoline-1,3-dione – 2-([{4-nitrophenyl}imino](phenyl)methyl)isoindoline-1,3-dione Iа. It belongs to the 5th class of toxicity – "practically non-toxic". Studies of biological activity in vivo have shown that compound Ia has pronounced analgesic and anti-inflammatory effects. Conclusion. It has been experimentally proved that 2-([{4-nitrophenyl}imino](phenyl)methyl)isoindoline-1,3-dione has low toxicity and exhibits pronounced analgesic and anti-inflammatory activity

computer prediction
acute toxicity
analgesic activity
anti-inflammatory activity
formalin edema

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