Evaluation of Hematotoxicity of New Derivatives of Condensed 3-Aminothieno[2,3-B]pyridines and 1,4-Dihydropyridines With High Analgesic Activity

Abstract

Pain is a significant problem in medicine today. More than 70% of diseases are accompanied by acute or chronic pain syndrome. According to the World Health Organization, pain syndromes are one of the most common reasons for seeking medical care, accounting for up to 40% of registered cases. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed around 500 million times every year. However, many patients with chronic pain rely on over-the-counter medications. Among the NSAIDs prescribed in clinical practice, hematotoxicity is a common adverse reaction. Objective: To assess changes in blood parameters in rats after a two-week administration of the most commonly used clinically NSAIDs and new derivatives of the 3-aminothieno[2,3-b]pyridine and 1,4-dihydronicotinamide series with the most pronounced analgesic activity. Methods: Ten low molecular weight ligands were chosen after screening various ligands. These ligands are capable of interacting with receptors and enzymes that are involved in the antinociceptive system. They contain fragments of 3-aminothieno[2,3-b]pyridine and 1,4-dihydronicotinamide. Samples with laboratory codes AZ023, AZ169, AZ213, AZ257, AZ729, AZ383, AZ331, AZ420, AU04271, AU04288 were selected for the experiment. Among them, AZ383, AZ331, AZ023, and AZ420 were chosen. The study involved 36 white male rats weighing between 250-280 g. Blood was collected via the femoral vein and analyzed using standard methods for erythrocyte, leukocyte, platelet, hemoglobin, and erythrocyte sedimentation rate (ESR) levels. Results: According to experimental studies, unlike the reference drug, the compounds studied do not cause leukopenia. In addition, only a tendency to decrease the number of platelets was detected for compounds AZ023, AZ331, and AZ383 with pronounced analgesic and anti-inflammatory activity, which requires additional research. Conclusion: Studies conducted on the safety of using derivatives of condensed 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines have shown promising results for further preclinical development. These derivatives can become highly effective and safe agents for alleviating pain and inflammation of various origins and severity in the future. Keywords: Blood test, hematotoxicity, pain syndrome, analgesic activity, thienopyridines, 1,4-dihydropyridine