Phytochemicals from Amaranthus tricolor L. with Potential Anti-Inflammatory Activity: An In Silico Molecular Docking, QSAR, and ADMET Study

Abstract

Inflammation is a complex biological response that contributes to the pathogenesis of many chronic diseases. Cyclooxygenase2 (COX-2) plays a central role in inflammatory processes by catalyzing the synthesis of proinflammatory prostaglandins. Natural COX-2 inhibitors have gained increasing interest as potential alternatives to synthetic drugs due to their improved safety profiles. Amaranthus tricolor L., a leafy vegetable, is traditionally recognized for its anti-inflammatory and antioxidant properties. This study investigated the anti-inflammatory potential of major phytochemicals from A. tricolor using an integrated in silico approach involving molecular docking, ADMET profiling, and quantitative structure–activity relationship (QSAR) analysis to identify promising COX2 inhibitors. A total of thirty-three phytocompounds reported in A. tricolor were identified and screened against the crystal structure of COX-2 enzyme (PDB: 1CX2) using molecular docking. Diclofenac was employed as a reference drug. Docking was performed using PyRx, binding interactions were visualized using BIOVIA Discovery Studio. The physicochemical, pharmacokinetic, drug-likeness properties of the top-scoring ligands were evaluated using SwissADME, admetSAR, ChemDes, and pkCSM. Docking results revealed that myricetin-3-O-rutinoside exhibited the strongest binding affinity (−10.2 kcal/mol), exceeding that of diclofenac (−7.0 kcal/mol), followed by myricetin (−9.9 kcal/mol), quercetin (−9.5 kcal/mol), and a few others. These compounds formed stable interactions with active-site residues of COX-2. ADMET and QSAR analyses indicated favorable absorption, moderate bioavailability, and acceptable safety profiles for most top ligands, while toxicity prediction suggested low hepatotoxicity and mutagenicity risks. The findings highlight myricetin, quercetin derivatives, and several other phytocompounds from A. tricolor as promising COX-2 inhibitors with potential anti-inflammatory activity.

Received: 23 December 2025 | Revised: 30 March 2026 | Accepted: 20 April 2026

Conflicts of Interest

The authors declare that they have no conflicts of interest to this work.

Data Availability Statement

All data generated or analyzed during this study are included in this published article.

Author Contribution Statement

Ferdousi Ahmed Sumona: Software, Investigation, Writing – original draft, Visualization. Sawda Binta Kamrul Oishi: Software, Formal analysis, Investigation, Writing – original draft, Visualization. Md. Rakibul Hossain: Formal analysis, Investigation, Writing – original draft, Visualization. Sumaiya Khatun: Formal analysis, Investigation, Writing – original draft, Visualization. Ayesha Islam Sadia: Formal analysis, Investigation, Writing – original draft, Visualization. Md. Sabbir Hossain: Formal analysis, Investigation, Writing – original draft, Visualization. Md. Abu Bakar Siddique Jami: Conceptualization, Methodology, Software, Resources, Data curation, Writing – original draft, Writing – review & editing, Visualization, Supervision, Project administration.