Browsing by Author "Zlatanova-Tenisheva H."

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    Anti-Inflammatory and Immunomodulatory Effects of 2-(3-Acetyl-5-(4-Chlorophenyl)-2-Methyl-1H-Pyrrol-1-yl)-3-Phenylpropanoic Acid
    (2025-08-01) Zlatanova-Tenisheva H.; Vladimirova S.
    Background: The pursuit of novel anti-inflammatory agents with enhanced efficacy and safety is crucial. Pyrrole-containing compounds, integral to many NSAIDs, exhibit promising anti-inflammatory properties. Compound 3f (2-(3-acetyl-5-(4-chlorophenyl)-2-methyl-1H-pyrrol-1-yl)-3-phenylpropanoic acid), a pyrrole derivative structurally inspired by the COX-2 selective inhibitor celecoxib, was evaluated for its anti-inflammatory and immunomodulatory effects. Methods: Anti-inflammatory activity was assessed in a carrageenan-induced paw edema model in Wistar rats. Compound 3f was administered intraperitoneally at 10, 20, and 40 mg/kg, either as a single dose or daily for 14 days. Diclofenac (25 mg/kg) served as the reference. Edema volume was measured by plethysmometry. Systemic inflammation was induced by lipopolysaccharide (LPS), and serum levels of the pro-inflammatory cytokine TNF-α and anti-inflammatory cytokines IL-10 and TGF-β1 were quantified by ELISA following single and repeated administration of compound 3f. Results: Single-dose administration of compound 3f at 20 mg/kg significantly reduced paw edema at 2 h (p = 0.001). After 14 days, all tested doses significantly inhibited paw edema at all time points (p < 0.001). In the LPS-induced systemic inflammation model, repeated treatment with 40 mg/kg of compound 3f significantly decreased serum TNF-α (p = 0.032). TGF-β1 levels increased significantly after both single and repeated doses (p = 0.002 and p = 0.045, respectively), while IL-10 levels remained unaffected. Conclusions: Compound 3f exhibits potent anti-inflammatory activity, particularly after repeated dosing, reflected by reduced local edema and systemic TNF-α suppression. The marked elevation of TGF-β1 indicates a potential immunomodulatory mechanism, selectively modulating cytokine profiles without altering IL-10. These findings support compound 3f as a promising candidate for targeted anti-inflammatory therapy involving cytokine regulation.
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    Experimental screening for analgesic and antiinflammatory effect of novel compounds with a pyrrole heterocycle
    (2024-01-01) Zlatanova-Tenisheva H.; Vladimirova S.
    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.
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    Synthesis and biological study of novel FELL analogs containing L- or d-tyr instead of l-phe in the N-terminus
    (2025-01-01) Borisova B.; Nocheva H.; Zlatanova-Tenisheva H.; Laronze-Cochard M.; Gérard S.; Danalev D.
    The high prevalence of pain affecting millions of people worldwide made it a major health problem. At the same time often, inflammation is closely associated to the pain. Thus, creation of molecules with a double effect is a good alternative to the currently existing in the medicinal practice non-steroidal medications. Herein, some modifications in the N- and C-terminus of the tetrapeptide FELL with proven anti-inflammatory properties are performed and the newly synthesized compounds are tested for both analgesic and anti-inflammatory potential. The analgesic and anti-inflammatory activity of the newly synthesized molecules was investigated using Paw-pressure and Carrageenan-Induced Paw Edema tests, respectively, on experimental animals. The results showed a certain “discrepancy” between the analgesic and the anti-inflammatory effects of the newly synthesized substances. Newly synthesized BB9 and BB15, L-Tyr containing C-terminal amide and free acid, respectively, exhibit a more significant analgesic activity compared to those of parent molecules BB1 and BB11, containing L-Phe in the N-terminus. Moreover, taking into account the obtained results for the compounds BB10 and BB16, the preferable substitution is L-Tyr, instead of D-Tyr. It could be concluded that the aromatic OH-function is probably important for the connection with the opioid and cannabinoid receptors. However, the designed structural modifications did not lead to improvement in anti-inflammatory effect compared to those of parent molecules. Moreover, in a context of the positive finding is that all modifications done save the hydrolytic stability of the molecules.