Synthesis and Study Anti-Inflammatory Activity of Nicotinic Acid Hydrazones

Objective: The aim of this study is to produce novel of the new functionally substituted nicotinohydrazones, analyze their anti-inflammatory activity, and assess their toxicity. A promising avenue for the advancement of novel bioactive compounds is the pursuit of “hybrid molecules” that contain pharmacophore fragments within their structural composition, with a particular focus on the examination of these molecules for the discovery of novel biological activities. Methods: The synthesis of nicotinic acid hydrazones (II–VI) was performed by condensation of nicotinic acid hydrazide with various aldehydes in ethanol when refluxing the reaction mixture at 60–70°C. The anti-inflammatory activity was studied using the formalin paw edema method in non-linear white rats. The acute inflammatory reaction was reproduced by subplantar (i.e., underplantar or plantar aponeurosis) injection of 0.1 mL of a 2% formalin solution into the right paw using a conventional insulin syringe. Results and Discussion: The structure of the new functionally substituted nicotinohydrazones has been confirmed by a combination of the 1H and 13C NMR methods, and COSY (1H-1H), HMQC (1H–13C), and HMBC (1H–13C) two-dimensional NMR spectroscopy methods.1H, and 13C NMR spectroscopy were used to investigate all the prepared derivatives. The acute toxicity of the aforementioned compounds was preliminarily evaluated using a specially developed Toxicity Assessment Software Tool within the United States Environmental Protection Agency. The LD50 values for rats following oral administration of the compounds tested by the QSAR method. According to the projected toxicological effects, compounds (II), (III) can be classified into Class 4 in terms of toxicity. Compounds (IV), (V) and (VI) have low toxicity and very low toxicity, respectively. Conclusions: The anti-inflammatory activity of the synthesized hydrazones has been evaluated and it has been demonstrated that these compounds were ineffective in comparison with ibuprofen at a dosage of 100 mg/kg (p2 < 0.05). The low toxicity level of all the tested compounds was predicted by the computer modeling. The LD50 values of the compounds range from 445.461 to 1491.991 mg/kg. The studies on the model of formalin paw edema in nonlinear white rats indicate the absence of an anti-inflammatory effect of the tested compounds.