biostudies-literatureSonuKing Khalid University Deanship of Scientific ResearchKing Khalid Universitye40300https://www.ebi.ac.uk/biostudies/studies/S-EPMC11617876biostudies-literatureUnknown10(22)<h4>Background</h4>The present study is aimed to investigate the anti-inflammatory activities of thirteen substituted-isoxazole derivatives (5a-5m). Isoxazole is a key pharmacophore in medicinal chemistry, known for its broad range of pharmacological activities.This study explores the synthesis and anti-inflammatory potential of thirteen substituted-isoxazole derivatives (5a-5m), with <b>5c, 5d, 5e,</b> and <b>5g</b> being novel compounds.<h4>Objectives</h4>The primary objectives were to synthesize some novel substituted isoxazole derivatives, evaluate their interaction with cyclooxygenase (COX-1/2) enzymes through computational methods, and assess their anti-inflammatory effectiveness in laboratory animals.<h4>Methods</h4>Substituted chalcones (0.01 mol) (2a-2m), sodium ethoxide (0.01 mol), and hydroxylamine hydrochloride (0.01 mol) were dissolved in absolute ethanol (15 ml), and then the mixture was refluxed for 6 h in an oil bath and monitored by TLC (ethyl acetate:hexane 7:3 v/v as eluent; a UV lamp was used to visualize the plates). After the completion of the reaction, as per TLC, the contents of the reaction mixture were poured into ice-cold water (50 ml). The obtained precipitates were filtered, washed two times, dried for 2 h at room temperature, and then recrystallized with ethenol. The structures of these compounds were confirmed via Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR) spectroscopy, carbon-13 nuclear magnetic resonance (¹³C NMR) spectroscopy, and mass spectrometry. Anti-inflammatory activity was evaluated using the carrageenan-induced rat paw edema method.<h4>Results</h4>The results indicated that three compounds (<b>5b, 5c,</b> and <b>5d</b>) demonstrated significant <i>in vivo</i> anti-inflammatory potential (% edema inhibition 75.68, 74.48, & 71.86 in 2 h and 76.71, 75.56, & 72.32 in 3 h) with modest effectiveness (0.83, 0.81 & 0.71), low toxicity, and minimal adverse effects. The molecular docking analyses further elucidated the interaction with the active site COX-2 enzyme (PDB ID: 4COX) using Autodock Vina. The compounds <b>5b, 5c,</b> and <b>5d</b> -8.7, -8.5, and -8.4 indicate good binding affinity (kcal/mol) and H-bond interaction with residues such as Cys41, Ala151, and Arg120 for COX-2, which also carried out RMSD values of 2.174, 41.13, and 22.25, which are decisive for the reported anti-inflammatory activity of diverse compounds.<h4>Conclusions</h4>The findings indicate that isoxazole derivatives have modest antiinflammatory potential, with compounds (<b>5b, 5c,</b> and <b>5d</b>) acting as lead molecules to be studied further for pain relief with fewer adverse effects.HeliyonSynthesis, characterization, molecular docking and pharmacological evaluation of isoxazole derivatives as potent anti-inflammatory agents.PMC11617876RGP2/580/45Singh HMishra AKSonuParveen BRSingh MYt KKumar AGautam GKfalseSynthesis, characterization, molecular docking and pharmacological evaluation of isoxazole derivatives as potent anti-inflammatory agents.<h4>Background</h4>The present study is aimed to investigate the anti-inflammatory activities of thirteen substituted-isoxazole derivatives (5a-5m). Isoxazole is a key pharmacophore in medicinal chemistry, known for its broad range of pharmacological activities.This study explores the synthesis and anti-inflammatory potential of thirteen substituted-isoxazole derivatives (5a-5m), with <b>5c, 5d, 5e,</b> and <b>5g</b> being novel compounds.<h4>Objectives</h4>The primary objectives were to synthesize some novel substituted isoxazole derivatives, evaluate their interaction with cyclooxygenase (COX-1/2) enzymes through computational methods, and assess their anti-inflammatory effectiveness in laboratory animals.<h4>Methods</h4>Substituted chalcones (0.01 mol) (2a-2m), sodium ethoxide (0.01 mol), and hydroxylamine hydrochloride (0.01 mol) were dissolved in absolute ethanol (15 ml), and then the mixture was refluxed for 6 h in an oil bath and monitored by TLC (ethyl acetate:hexane 7:3 v/v as eluent; a UV lamp was used to visualize the plates). After the completion of the reaction, as per TLC, the contents of the reaction mixture were poured into ice-cold water (50 ml). The obtained precipitates were filtered, washed two times, dried for 2 h at room temperature, and then recrystallized with ethenol. The structures of these compounds were confirmed via Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR) spectroscopy, carbon-13 nuclear magnetic resonance (¹³C NMR) spectroscopy, and mass spectrometry. Anti-inflammatory activity was evaluated using the carrageenan-induced rat paw edema method.<h4>Results</h4>The results indicated that three compounds (<b>5b, 5c,</b> and <b>5d</b>) demonstrated significant <i>in vivo</i> anti-inflammatory potential (% edema inhibition 75.68, 74.48, & 71.86 in 2 h and 76.71, 75.56, & 72.32 in 3 h) with modest effectiveness (0.83, 0.81 & 0.71), low toxicity, and minimal adverse effects. The molecular docking analyses further elucidated the interaction with the active site COX-2 enzyme (PDB ID: 4COX) using Autodock Vina. The compounds <b>5b, 5c,</b> and <b>5d</b> -8.7, -8.5, and -8.4 indicate good binding affinity (kcal/mol) and H-bond interaction with residues such as Cys41, Ala151, and Arg120 for COX-2, which also carried out RMSD values of 2.174, 41.13, and 22.25, which are decisive for the reported anti-inflammatory activity of diverse compounds.<h4>Conclusions</h4>The findings indicate that isoxazole derivatives have modest antiinflammatory potential, with compounds (<b>5b, 5c,</b> and <b>5d</b>) acting as lead molecules to be studied further for pain relief with fewer adverse effects.2024-01-01T00:00:00Z2024 Nov2026-06-02T03:37:58.601Z2025-04-04T01:57:42.472ZS-EPMC116178763964107510.1016/j.heliyon.2024.e40300