Pharmacological Evaluation of Novel Hydrazide and Hydrazone Derivatives: Anti-Inflammatory and Analgesic Potential in Preclinical Models

• Published in: Molecules
• Main Authors: Hristina Zlatanova-Tenisheva, Stanislava Vladimirova
• Format: Article
• Language: English
• Published: MDPI AG 2025-03-01
• Subjects: hydrazones; tail-flick; paw withdrawal; formalin model; paw edema
• Online Access: https://www.mdpi.com/1420-3049/30/7/1472

Hydrazones, characterized by their C=N–NH functional group, are promising candidates in medicinal chemistry due to their ability to interact with biological targets. This study evaluated the anti-inflammatory and analgesic properties of <i>N</i>-pyrrolylcarbohydrazide (<b>1</b>) and four pyrrole hydrazone derivatives (<b>1A–D</b>) in male Wistar rats (6 weeks old). Anti-inflammatory activity was assessed using a carrageenan-induced paw edema model, while formalin, tail flick, and paw withdrawal tests evaluated analgesia. Compound <b>1</b> exhibited dose-dependent anti-inflammatory activity. At 20 mg/kg, significant edema reductions were observed at the 2nd (<i>p</i> = 0.035) and 3rd hours (<i>p</i> = 0.022), while at 40 mg/kg, reductions remained significant at the 2nd (<i>p</i> = 0.008) and 3rd hours (<i>p</i> = 0.046). Compound <b>1A</b> showed pronounced effects at 20 mg/kg at the 2nd (<i>p</i> = 0.005), 3rd (<i>p</i> < 0.001), and 4th hours (<i>p</i> = 0.004). Other compounds demonstrated minimal or no activity. Analgesic evaluation revealed that at 40 mg/kg, compound <b>1</b> significantly reduced paw-licking time in the second phase (<i>p</i> = 0.038). Compounds <b>1B</b>, <b>1C</b>, and <b>1D</b> exhibited transient effects in the first phase only (<i>p</i> < 0.05). Compound <b>1A</b> lacked significant analgesic activity. The findings suggest that structural modifications may enhance efficacy for broader therapeutic applications.