Synthesis, computational profiling, and anti-inflammatory potential of a thymol-mefenamic acid hybrid derivative
Year: 2025
Type: article
Abstract: Natural products, particularly terpenoids from aromatic plants like Thymus vulgaris L., hold significant potential in anti-inflammatory drug discovery. This study aimed to isolate bioactive terpenoids, synthesize ester derivative (R1) by reacting thymol with mefenamic acid, and evaluate its anti-inflammatory efficacy. Essential oils were extracted via steam distillation, and thymol (26.35%) was identified as the major component using GC-MS. R1 (2-isopropyl-5-methylphenyl 2-((2,3-dimethylphenyl)amino)benzoate) was synthesized via DCC/DMAP-mediated esterification, purified by column chromatography, and characterized by Fourier transform infrared (FT-IR), NMR, and mass spectrometry. Density functional theory (DFT) at B3LYP/6–31G(d,p) optimized R1’s geometry, while molecular docking (AutoDock 4.2.3) revealed strong binding affinities (−8.60 kcal/mol with TNF-α [PDB:2az5]; −6.20 kcal/mol with IL-6 [PDB:1alu]). Molecular dynamics (MD) simulations indicated complex stability via hydrogen bonds and hydrophobic interactions. In vitro assays on 3T3-L1 adipocytes demonstrated dose-dependent inhibition of pro-inflammatory cytokines: R1 (10 µg/mL) reduced TNF-α by 29.77% and IL-6 by 39.56%, though less potent than dexamethasone. Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions highlighted R1’s drug-likeness (Lipinski/Veber compliance) but noted hepatotoxicity and hERG inhibition risks. Spectroscopic and computational data aligned, validating R1’s structure and reactivity. These findings position R1 as a promising anti-inflammatory lead, warranting further in vivo studies to optimize efficacy and safety.
Source: Figshare
Authors: Arya, Manish, Jaiswal, Mayank, Ram, Anant, Chaubey, Shiwa, Gautam, Saurabh Kumar, Singh, Kalpana, Anupam, Singh, Santosh Kumar
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W6902228768
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