QSAR study of the DPPH· radical scavenging activity of coumarin derivatives and xanthine oxidase inhibition by molecular docking

• Published in: Central European journal of chemistry 2014-10, Vol.12 (10), p.1067-1080
• Main Authors: Razo-Hernández, Rodrigo S., Pineda-Urbina, Kayim, Velazco-Medel, Marlene A., Villanueva-García, Manuel, Sumaya-Martínez, M. Teresa, Martínez-Martínez, Francisco J., Gómez-Sandoval, Zeferino
• Format: Article
• Language: English
• Subjects: Antioxidants; Biochemistry; Biological and Medical Physics; Biophysics; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Coumarin; Coumarins; Derivatives; Docking; DPPH; Geochemistry; Inhibition; Mathematical models; QSAR; Radicals; Research Article; Xanthine Oxidase
• ISSN: 1895-1066; 2391-5420; 1644-3624; 2391-5420
• DOI: 10.2478/s11532-014-0555-x

A Quantitative Structure-Activity Relationship (QSAR) of coumarins by genetic algorithms employing physicochemical, topological, lipophilic and electronic descriptors was performed. We have used experimental antioxidant activities of specific coumarin derivatives against the DPPH· radical molecule. Molecular descriptors such as Randic Path/Walk, hydrophilic factor and chemical hardness were selected to propose a mathematical model. We obtained a linear correlation with R 2 = 96.65 and Q LOO 2 = 93.14 values. The evaluation of the predictive ability of the model was performed by applying the Q ASYM 2 , and Δ r m 2 methods. Fukui functions were calculated here for coumarin derivatives in order to delve into the mechanics by which they work as primary antioxidants. We also investigated xanthine oxidase inhibition with these coumarins by molecular docking. Our results show that hydrophobic, electrostatic and hydrogen bond interactions are crucial in the inhibition of xanthine oxidase by coumarins.