SYNTHESIS, CHARACTERIZATION, AND INITIAL PHARMACOLOGICAL ASSESSMENT OF NEW NAPROXEN WITH 1,3,4-THIADIAZOL-2-AMINE DERIVATIVES

Ghanim Ali Mahdi; Zainab Abdelhadi Dakhel

doi:10.46903/gjms/22.03.1675

SYNTHESIS, CHARACTERIZATION, AND INITIAL PHARMACOLOGICAL ASSESSMENT OF NEW NAPROXEN WITH 1,3,4-THIADIAZOL-2-AMINE DERIVATIVES

Ghanim Ali Mahdi, Zainab Abdelhadi Dakhel

Abstract

Background: Phosphorous oxychloride (POCl3) was employed as a catalyst in this particular research to facilitate the reaction between naproxen and thiosemicarbazide. The main objective of this study was to synthesize four distinct compounds, namely naproxen with 1,3,4-thiadiazol-2-amine moiety derivatives followed by N-alkylation, denoted as Gh5, Gh6, Gh7, and Gh8. This study aimed to synthesize and characterize novel naproxen derivatives and evaluate their anti-inflammatory efficacy. A molecular docking analysis was conducted on the newly synthesized compounds against the binding pocket of receptor for COX-2 to predict their potential activity.

Materials & Methods: The synthesis of the compounds involved the reaction of naproxen and thiosemicarbazide in the presence of POCl3. The resulting products, Gh5, Gh6, Gh7, and Gh8, were subjected to FT-IR and 1H NMR spectroscopy for comprehensive characterization. Additionally, the anti-inflammatory efficacy of the compounds was assessed in vivo using paw edema tests in Albino rats induced by egg whites. The evaluation involved comparing the effectiveness of the synthesized compounds with naproxen as the reference substance and DMSO serving as a control and solvent.

Results: The results of the anti-inflammatory effectiveness assessment revealed that the formulated compounds exhibited noteworthy properties in alleviating induced paw edema in Albino rats, demonstrating efficacy comparable to that of the reference compound. The experimental findings suggested that the synthesized compounds might even exhibit superior anti-inflammatory effects compared to the reference compound. The molecular docking analysis provided insights into the potential interactions within the COX-2 binding pocket, supporting the observed biological activity.

Conclusion: The synthesized naproxen derivatives, Gh5, Gh6, Gh7, and Gh8, exhibited significant anti-inflammatory properties, potentially surpassing the effectiveness of naproxen. These findings highlight the promising potential of these compounds for further exploration in anti-inflammatory research.

Keywords

Nonsteroidal anti-inflammatory drugs; Heterocyclic compounds; 1,3,4-thiadiazole; Naproxen; thiosemicarbazide.

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DOI: https://doi.org/10.46903/gjms/22.03.1675