원문정보
초록
영어
Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organsincluding the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMSIA) on a series of 2-(indol- 5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMSIA models were generated based on atom-by- atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMSIA models were generated using different alignments and the best model yielded across- validated q2 of 0.698 with five components and non-cross-validated correlation coefficient (r2) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMSIA models was found to be r2 pred 0.653. The study revealed the important structural features required for the biological activity of the inhibitors and could provide useful for the designing of novel and potent drugs for the inhibition of Xanthine oxidase.
목차
1. Introduction
2. Materials and Methods
2.1. Data Set
2.2. Partial Atomic Charge Calculation and Bioactive Conformation Determination
2.3. CoMSIA Model Calculation
2.4. Partial Least Squares (PLS) Analysis
2.5. Predictive Correlation Coefficient (r2 pred)
2.6. CoMSIA Contour Maps
3. Results and Discussion
3.1. CoMSIA Model Analysis
3.2. Mapping of CoMSIA Contour Maps
4. Conclusion
References