Design and evaluation of novel triazole derivatives as potential anti-gout inhibitors: a comprehensive molecular modeling study DOI Creative Commons
Mohammed Er-rajy, Mohamed El fadili, Sara Zarougui

и другие.

Frontiers in Chemistry, Год журнала: 2025, Номер 13

Опубликована: Март 6, 2025

Gout is the most common inflammatory arthritis, characterized by hyperuricemia, tophus formation, joint disease, and kidney stones. Uric acid, final byproduct of purine catabolism, eliminated via kidneys digestive system. Xanthine oxidase (XO) catalyzes conversion hypoxanthine xanthine into uric making XO inhibitors crucial for treating hyperuricemia gout. Currently, three are clinically used, showing significant efficacy. A molecular modeling study on triazole derivatives aims to identify novel using 3D-QSAR, docking, MD simulations, ADMET analysis, DFT calculations. These computational approaches facilitate drug discovery while reducing research costs. Our work focuses a series synthesized anti-xanthine inhibitors, aiming develop new inhibitors. was carried out inhibitory structural features method. model based CoMFA CoMSIA/SEA has been built predict derivatives. The optimal established from successfully evaluated its predictive capability. Visualization contour maps both models showed that modifying substituents plays key role in enhancing biological activity anti-gout Molecular docking results complexes N°8-3NVY N°22-3NVY scores -7.22 kcal/mol -8.36 kcal/mol, respectively, indicating substantial affinity enzyme. Complex forms two hydrogen bonds with SER 69 ASN 71, alkyl ALA 70, LEU 74, 75, one Pi-Pi T-shaped bond PHE 68. HIS 99, ARG 29, ILE 91, halogen 128 at 3.60 Å. revealed complex remained highly stable throughout simulation. Therefore, we proposed six molecules, their activities were predicted models, they Lipinski's rule, properties. show Pred 4 5 have better pharmacokinetic properties than height potent molecule studied series, these compounds valuable candidates drugs. Subsequently, evaluate chemical reactivity compounds, energy gap molecules exhibit moderate stability reactivity.

Язык: Английский

Design and evaluation of novel triazole derivatives as potential anti-gout inhibitors: a comprehensive molecular modeling study DOI Creative Commons
Mohammed Er-rajy, Mohamed El fadili, Sara Zarougui

и другие.

Frontiers in Chemistry, Год журнала: 2025, Номер 13

Опубликована: Март 6, 2025

Gout is the most common inflammatory arthritis, characterized by hyperuricemia, tophus formation, joint disease, and kidney stones. Uric acid, final byproduct of purine catabolism, eliminated via kidneys digestive system. Xanthine oxidase (XO) catalyzes conversion hypoxanthine xanthine into uric making XO inhibitors crucial for treating hyperuricemia gout. Currently, three are clinically used, showing significant efficacy. A molecular modeling study on triazole derivatives aims to identify novel using 3D-QSAR, docking, MD simulations, ADMET analysis, DFT calculations. These computational approaches facilitate drug discovery while reducing research costs. Our work focuses a series synthesized anti-xanthine inhibitors, aiming develop new inhibitors. was carried out inhibitory structural features method. model based CoMFA CoMSIA/SEA has been built predict derivatives. The optimal established from successfully evaluated its predictive capability. Visualization contour maps both models showed that modifying substituents plays key role in enhancing biological activity anti-gout Molecular docking results complexes N°8-3NVY N°22-3NVY scores -7.22 kcal/mol -8.36 kcal/mol, respectively, indicating substantial affinity enzyme. Complex forms two hydrogen bonds with SER 69 ASN 71, alkyl ALA 70, LEU 74, 75, one Pi-Pi T-shaped bond PHE 68. HIS 99, ARG 29, ILE 91, halogen 128 at 3.60 Å. revealed complex remained highly stable throughout simulation. Therefore, we proposed six molecules, their activities were predicted models, they Lipinski's rule, properties. show Pred 4 5 have better pharmacokinetic properties than height potent molecule studied series, these compounds valuable candidates drugs. Subsequently, evaluate chemical reactivity compounds, energy gap molecules exhibit moderate stability reactivity.

Язык: Английский

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