Anti-inflammatory and antinociceptive activity of indenopyrroles and indenopyridazines in the experiment

Background. Currently, the main groups of anti-inflammatory drugs used in medical practice are steroidal (glucocorticoids) and non-steroidal agents. However, despite their widespread use, these groups of anti-inflammatory drugs have a fairly wide range of negative side effects, which makes the search for low-toxic substances with anti-inflammatory effects currently relevant.

The aim. To study anti-inflammatory, antinociceptive activity and acute toxicity of individual representatives of indenopyrroles and indenopyridazines.

Methods. The acute toxicity of the studied compounds was studied using the method of Prozorovsky VB. Anti-inflammatory activity was assessed in a carrageenan-induced rat paw edema model. The production of active oxygen radicals by leukocytes was evaluated using luminol-dependent chemiluminescence. The antinociceptive activity of the compounds was assessed using the “writhing” and “hot plate” tests in mice.

Results. The obtained results allowed the studied compounds to be classified as “practically nontoxic” (LD50 > 1000 mg/kg). Compounds 1в of the indenopyrrole series and indenopyridazines 2а-в were found to exhibit anti-inflammatory activity, reducing the severity of exudative inflammation. Compound 2a exhibited the greatest antiexudative activity, reducing edema by more than 60 % (p < 0.01). Compounds 2a-в and compound 1в reduced the production of reactive oxygen species by more than 40 % (p < 0.05) compared to the control. In the “hot plate” test, the studied compounds 1a, 1в, 2a-в exhibited an antinociceptive effect comparable to nimesulide; in the “acetic acid-induced writhing” test, the effect of compounds 1a, 2б, 2в was comparable to nimesulide, and the effect of compound 2a exceeded the comparison drug by 32.96 % (p < 0.05).

Conclusion. The studied compounds of the indenopyrrole series and their indenopyridazine derivatives are virtually non-toxic compounds, exhibit an anti-inflammatory effect and reduce the severity of pain associated with inflammation.

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