In silico analysis of the anti-inflammatory activity of curcuminoids and/or curcumin metabolites on Cox-1 and Cox-2

Abstract

Background The present work involved a comparative in silico analysis of the action of curcuminoids and curcumin metabolites against cyclooxygenases 1 and 2. The Protein Data Bank (PDB) was used to obtain the target proteins and Discovery studio 2021, PyRx, ChemDraw Professional 16.0 or the PubChem search engine were used during in silico screening. Results The in silico analyses revealed that all the ligands analyzed form stable complexes with the Cox-1 and Cox-2 receptors, which are involved in anti-inflammatory activity. The complexation energy of the ligands with Cox-1 ranged from − 7.2 to -8.8 kcal/mol. The complexation energy of Cox-2 and the ligands analyzed ranged from − 5.2 to -6.4 kcal/mol, predicting a high affinity between the ligands analyzed and Cox-1 compared with Cox-2. In addition, the ligands analyzed formed thermodynamically stable complexes with Cox-1 in the majority of cases compared to the reference molecules analyzed (aspirin: -6.2 Kcal/mol and ibuprofen: -7.2 Kcal/mol). Bisdemethoxycurcumin, curcumin sulphate, curcumin, cyclocurcumin, demethoxycurcumin, dihydrocurcumin, hexahydrocurcumin and tetrahydrocurcumin formed very stable bonds with Cox-1 with interaction enthalpies of -8, 8 Kcal/mol, -8.7 Kcal/mol, -8.6 Kcal/mol, -8.3 Kcal/mol, -8.3 Kcal, -8.0 Kcal/mol, -7.9 Kcal/mol and − 7.8 Kcal/mol respectively. Moreover, most of the ligands analyzed formed thermodynamically stable bonds with Cox-2 compared with the reference molecules. The binding enthalpies were − 6.4 Kcal/mol, -6.1 Kcal/mol; -6.1 Kcal/mol, -5.9 Kcal/mol, -5.9 Kcal/mol, -5.7 Kcal/mol, -5.6 Kcal/mol and − 5.5 Kcal/mol for cyclocurcumin, bisdemethoxycurcumin, demethoxycurcumin, curcumin, curcumin sulphate, glucuronocurcumin, dihydrocurcumin and tetrahydrocurcumin respectively; compared with 4.5 Kcal/mol for the complex formed with aspirin and − 5.4 Kcal/mol for that formed with ibuprofen. Conclusion Curcuminoids can individually or synergistically inhibit the action of Cox and act as anti-inflammatory agents, curcumin metabolites can also bind to the catalytic sites of Cox 1 and 2 and compete with arachidonic acid, the natural substrate of Cox.