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

Abstract

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 N-pyrrolylcarbohydrazide (1) and four pyrrole hydrazone derivatives (1A-D) 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 1 exhibited dose-dependent anti-inflammatory activity. At 20 mg/kg, significant edema reductions were observed at the 2nd (p = 0.035) and 3rd hours (p = 0.022), while at 40 mg/kg, reductions remained significant at the 2nd (p = 0.008) and 3rd hours (p = 0.046). Compound 1A showed pronounced effects at 20 mg/kg at the 2nd (p = 0.005), 3rd (p < 0.001), and 4th hours (p = 0.004). Other compounds demonstrated minimal or no activity. Analgesic evaluation revealed that at 40 mg/kg, compound 1 significantly reduced paw-licking time in the second phase (p = 0.038). Compounds 1B, 1C, and 1D exhibited transient effects in the first phase only (p < 0.05). Compound 1A lacked significant analgesic activity. The findings suggest that structural modifications may enhance efficacy for broader therapeutic applications.

Keywords: formalin model; hydrazones; paw edema; paw withdrawal; tail-flick.

Figure 1

Comparison of edema percentage in carrageenan-induced paw edema model between saline and positive control groups and compound 1. * p < 0.001 compared to control, # p < 0.05 compared to control.

Figure 2

Comparison of edema percentage in carrageenan-induced paw edema model between saline and positive control groups and compound 1A. * p < 0.001 compared to control, # p < 0.05 compared to control.

Figure 3

Comparison of the time spent licking/biting paw (in seconds) in formalin test between saline and positive control, and compounds 1, 1B, 1C, and 1D. * p < 0.001 compared to control, # p < 0.05 compared to control.

Figure 4

Mechanisms of inflammation and hypothesized action of newly synthesized compounds.

Figure 5

Synthesis pathway of target compounds.