Synthesis and evaluation of analgesic, behavioral effects and chronic toxicity of the new 3,5-diaminopyrazole and its precursor the thiocyanoacetamide

Ali, Ridha Ben; Othman, Amal Ben; Bokri, Khouloud; Maghraoui, Samira; Hajri, Adel; Akacha, Azaiez Ben; Dziri, Chadli; May, Michèle Véronique El

doi:10.1016/j.biopha.2016.11.119

Cited by 14 publications

(7 citation statements)

References 26 publications

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“…After the tissue was embedded in paraffin and sectioned at the 5-µm thickness, sections were dyed with H&E according to the procedure. Photomicrographs were taken with a Nikon light microscope at 200X magnification, and the semi-quantitative toxicological evaluation was performed according to the comparison of the structural changes of the H&E results, as described by Ben et al 29 , 30 . Each organ tissue resulted in 10 images.…”

Section: Methodsmentioning

confidence: 99%

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Singh

Wang

et al. 2023

Int. J. Biol. Sci.

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Pain is the major reason that patients suffering from osteoarthritis (OA) seek medical care. We found that vascular endothelial growth factors (VEGFs) mediate signaling in OA pain pathways. To determine the specific contributions of VEGFs and their receptors (VEGFRs) to joint pathology and pain transmission during OA progression, we studied intra-articular (IA) injections of VEGF ligands into murine knee joints. Only VEGF ligands specific for the activation of VEGFR1, but not VEGFR2, induced allodynia within 30 min. Interventions in OA by inhibitors of VEGFRs were done in vivo using a preclinical murine OA model by IA injections of selective inhibitors of VEGFR1/VEGFR2 kinase (pazopanib) or VEGFR2 kinase (vandetanib). OA phenotypes were evaluated using pain-associated murine behavioral tests and histopathologic analyses. Alterations in VEGF/VEGFR signaling by drugs were determined in knee joints, dorsal root ganglia, and spinal cord by immunofluorescence microscopy. Pazopanib immediately relieved OA pain by interfering with pain transmission pathways. Pain reduction by vandetanib was mainly due to the inhibition of cartilage degeneration by suppressing VEGFR2 expression. In conclusion, IA administration of pazopanib, which simultaneously inhibits VEGFR1 and VEGFR2, can be developed as an ideal OA disease-modifying drug that rapidly reduces joint pain and simultaneously inhibits cartilage degeneration.

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Section: Methodsmentioning

confidence: 99%

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Singh

Wang

et al. 2023

Int. J. Biol. Sci.

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“…1). 2 Hoffmann-La Roche patented 5-amino-3-arylaminopyrazoles (e.g. 2) as antiviral agents, particularly useful for the treatment of hepatitis C virus infection.…”

Section: -Aminopyrazoles Have Been Well Recognised As Biologically Amentioning

confidence: 99%

A new practical synthesis of 3-amino-substituted 5-aminopyrazoles and their tautomerism

et al. 2019

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It was found that 3-amino-substituted 5-aminopyrazoles could be effectively prepared via hydrolytic decarboxylation of the corresponding 3,5-diaminopyrazole-4-carboxylates 5 under microwave irradiation. The reactions required short time (4 min) and were successfully reproduced in a larger scale and under conventional heating mimicking the microwave heating pattern. X-ray crystallography identified two different types of tautomers in crystals of related 5-aminopyrazoles with p-toluidyl and p-anisidyl moieties at the position 3, respectively.

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“…16 This Thm compound presents high analgesic effects proved by a complete absence of pain sensation during a strong tail pinch. 15 But, the antinociceptive effect and pharmacological mechanisms of this promising compound have not yet been studied. The present study warrants further investigations involving this novel molecule for the possible…”

Section: Introductionmentioning

confidence: 99%

“…It was also used to prevent doxorubicin‐induced damage of the gonads and spermatozoa in rats 16 . This Thm compound presents high analgesic effects proved by a complete absence of pain sensation during a strong tail pinch 15 …”

Section: Introductionmentioning

confidence: 99%

“…14 It has been reported that the new synthetic compound of thiocyanoacetamide (Thm) exhibits an excellent safety profile and important antioxidant capacity at low concentrations. 15 It was also used to prevent doxorubicin-induced damage of the gonads and spermatozoa in rats. 16 This Thm compound presents high analgesic effects proved by a complete absence of pain sensation during a strong tail pinch.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of antinociceptive effect and pharmacological mechanisms of thiocyanoacetamide in rats

et al. 2023

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ObjectiveAcute pain is the most common type of pain. The aim of the present work was carried out to study the antinociceptive effect and pharmacological mechanisms of thiocyanoacetamide (Thm) in rats exposed to thermal pain stimulus.Materials and MethodsThe anti‐nociceptive effect of the newly synthesized compound, Thm was studied in comparison to that of paracetamol (Para), dexamethasone (Dex), and morphine (Morph) at different doses using a hot plate test at a constant temperature of 48.0 ± 0.5°C. During this test, the latency time (LT) was measured when rats express pain behavior. Then, the pharmacological mechanisms were determined using receptor‐antagonist drugs.ResultsFirstly, the obtained result showed pain modulation of the pretreated rats with Thm at 10 mg/kg dose proved by the delay of latency time during the thermal test. This significant antinociceptive activity of the thiocyanoacetamide was more effective than that of paracetamol or dexamethasone and less than that of morphine. Second, the pretreatment with acebutolol or risperidone antagonist drugs of, respectively, adrenergic and serotonin receptors demonstrated the elimination of pain modulation with Thm 10 mg/kg dose proved by a short latency time of rat's response in hot plate test. In this case, the pharmacological mechanism of Thm was characterized by the involvement of adrenergic and serotoninergic systems.ConclusionsIt may be concluded that Thm constitutes a promising antinociceptive drug including beta‐adrenergic and serotoninergic targets. The present study warrants further investigation to determine the side effects of this compound.

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Synthesis and evaluation of analgesic, behavioral effects and chronic toxicity of the new 3,5-diaminopyrazole and its precursor the thiocyanoacetamide

Cited by 14 publications

References 26 publications

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

A new practical synthesis of 3-amino-substituted 5-aminopyrazoles and their tautomerism

Evaluation of antinociceptive effect and pharmacological mechanisms of thiocyanoacetamide in rats

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