New halogenated chalcones as potential anti-inflammatory agents: A comprehensive In-Silico, In-Vitro, and In-Vivo study with ADME profiling

• Published in: Journal of Molecular Structure
• Main Author: Iqtadar R.; Naz A.; Shah S.A.A.; Ali S.; Abdullah S.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2025
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85212427663&doi=10.1016%2fj.molstruc.2024.141055&partnerID=40&md5=b58724c26ca202294ee4b0ab908b7606

This study explored the anti-inflammatory potential of halogenated chalcone derivatives using in-silico, in-vitro and in-vivo models. The synthesized compounds were assessed for their ability to inhibit reactive oxygen species (ROS) production and their interaction with the cyclooxygenase-1 (COX-1) enzyme, a target of nonsteroidal anti-inflammatory drugs (NSAIDs). In-vitro assays demonstrated that these chalcone derivatives effectively reduced ROS levels, suggesting robust anti-inflammatory activity. This was further supported by in-vivo findings from the rat paw edema model, where treated groups exhibited a significant reduction in paw thickness compared to controls. Histopathological analysis confirmed a decrease in leukocyte infiltration in the treated groups, aligning with the observed anti-inflammatory effects. Molecular docking studies indicated strong binding affinities of the chalcone derivatives to the COX-1 enzyme, implying a similar mechanism of action to established NSAIDs like ibuprofen. Additionally, in-silico ADME (absorption, distribution, metabolism and excretion) profiling revealed favorable pharmacokinetic and drug-like properties, highlighting the therapeutic potential of these compounds. Overall, halogenated chalcone derivatives show promising anti-inflammatory properties through ROS inhibition and COX-1 binding, warranting further research to optimize their efficacy and validate their potential as new anti-inflammatory agents. © 2024 Elsevier B.V.