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.

EVALUATION OF A GROUP OF PYRROLE DERIVATIVES AS TUBERCULOSTATIC AGENTS

Background: Bioconjugates are promising alternatives for the multiple targeting of any disease. Pyrrole heterocycle is well known with many activities and is a building block of a lot of medical drugs. On the other hand, peptides are short molecules with many advantages such as small size, ability to penetrate the cell membrane and bond-specific receptors, vectorizing potential, etc. Thus, hybrid molecules between peptide and pyrrole moiety could be a promising alternative as an anti-pain tool. Methods: New bioconjugates with a general formula Pyrrole (α-/β-acid)-FELL-OH (NH₂) were synthesized using Fmoc/OtBu peptide synthesis on solid support. HPLC was used to monitor the purity of newly synthesized bioconjugates. Their structures were proven by electrospray ionization mass spectrometry. The Paw Pressure test (Randall–Selitto test) was used to examinate the analgesic activity. Hydrolytic stability of targeted structures was monitored in three model systems with pH 2.0, 7.4 and 9.0, including specific enzymes by means of the HPLC-UV method. Results: The obtained results reveal that all newly synthesized bioconjugates have analgesic activity according to the used test but free pyrrole acids have the best analgesic activity. Conclusions: Although free pyrrole acids showed the best analgesic activity, they are the most unstable for hydrolysis. Combination with peptide structure leads to the hydrolytic stabilization of the bioconjugates, albeit with slightly reduced activity.

Novel pyrrole-based carbohydrazide (1) and hydrazones (1A–D) were synthesized, characterized, and subjected to spectroscopic studies. The hydrazones were obtained by reacting a pyrrole hydrazide with substituted pyrrole aldehydes. The initial carbohydrazide was prepared by selective hydrazinolysis of the obtained N-pyrrolylcarboxylic acid ethyl ester. The biological activity of the newly synthesized compounds was investigated in vitro on a panel of tumor and non-tumor cell lines. Mouse embryonic fibroblasts BALB 3T3 clone A31 were used in the safety test (BALB 3T3 NRU-assay). Antiproliferative activity was determined on keratinocytes (HaCaT) and melanoma (SH-4) cells by MTT dye reduction assay. The safety test of the compounds showed low cytotoxicity and absence of phototoxic potential. Among our novel pyrrole hydrazones, 1C was the most selective (SI = 3.83) in human melanoma cells and exhibited very good antiproliferative activity (IC₅₀ = 44.63 ± 3.51 μM). The cytotoxic effect of 1C correlates with its ability to induce apoptosis and to cause cell cycle arrest in the S phase. In addition, the results show that hydrazones obtained by condensation with β-aldehydes are more bioactive than those obtained by condensation with α-aldehydes.

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The pyrrole heterocycle is found in the chemical structure of numerous drugs with various effects, and it has a reasonably high tolerance and safety profile. The objectives of our study were to assess the analgesic and anti-inflammatory efficacy of six novel compounds with pyrrolic structures. Methods: All trials were carried out on 6-week-old male Wistar rats. Animal pain models using thermal (paw withdrawal, tail-flick) and chemical stimuli (formalin test) were used to examine antinociception. A carrageenan-induced paw edema model was used to assess anti-inflammatory activity. Results: Significant differences between the experimental groups were observed in both early and late phase of the formalin test. Conclusions: The six novel pyrrolic compounds have analgesic action against chemical stimuli in experimental conditions. They do not possess anti-inflammatory activity, or antinociceptive properties against thermal stimuli.