In Silico Molecular Modelling and Dynamic Simulations, ADME Parameters Predictions of new Naproxen Analogues Containing 1,3,4-Oxadiazole as Anti-inflammatory Agents

Year 2025, Volume: 9 Issue: 4, 15 - 28

Farooq Algaragoolee , Ayad Kareem , Shakir Mahmood Alwan

Abstract

The serious challenges associated with the non-steroidal anti-inflammatory drugs (NSAIDs), especially their unfavorable impacts on the gastrointestinal tract (GIT)and kidneys arise from restraining cyclooxygenase (COX) enzymes. To address this issue and manage the side effects, several investigations were employed by modifying and adjusting the free carboxyl group of NSAIDs to upgrade their safety profile, while, keeping up their anti-inflammatory adequacy. An approach of suggesting new analogues of NSAIDS focusing on COX-2 enzyme devoid of side effects on stomach or kidneys is highly recommended. In this respect, the design of new analogues of naproxen is investigated by insertion of the carboxylic group into a 1,3,4-oxadiazole ring structure. This chemical modification points to hold anti-inflammatory impacts, whereas decreasing the hazard of stomach irritation and ulceration. These analogues were evaluated by means of computational methods, such as molecular docking, virtual screening, ADME (absorption, distribution, metabolism, and excretion) and molecular dynamics. The proposed compounds exhibited encouraging binding affinities to the COX-2 receptor, as demonstrated by molecular docking and molecular dynamic simulations. This may suggest that these compounds have the potential to be effective anti-inflammatory agents. Moreover, in silico ADME appraisals showed favorable pharmacokinetic profiles for the compounds that may suggest safer choices to known NSAIDs. Virtual evaluations of the new naproxen analogues have indicated their anti-inflammatory activity. These evaluations and the promising binding affinities and favorable pharmacokinetic profiles bolster the basis for advance preclinical and clinical ponders to approve the high potential of these compounds. Molecular dynamics simulations provide experiences into the energetic stability of the protein-ligand complex, with RMSD and RMSF investigations demonstrate steady interactions during time. This chemical modification offers a promising approach for the development of safer anti-inflammatory analogues of naproxen.

Keywords

Naproxen, 1,3,4-oxadiazole, Anti-inflammatory agents, ADME, Molecular dynamic

References

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