Development of a human dihydroorotate dehydrogenase (hDHODH) pharma-similarity index approach with scaffold-hopping strategy for the design of novel potential inhibitors.

ABSTRACT: Human dihydroorotate dehydrogenase (hDHODH) is a class-2 dihydroorotate dehydrogenase. Because it is extensively used by proliferating cells, its inhibition in autoimmune and inflammatory diseases, cancers, and multiple sclerosis is of substantial clinical importance. In this study, we had two aims. The first was to develop an hDHODH pharma-similarity index approach (PhSIA) using integrated molecular dynamics calculations, pharmacophore hypothesis, and comparative molecular similarity index analysis (CoMSIA) contour information techniques. The approach, for the discovery and design of novel inhibitors, was based on 25 diverse known hDHODH inhibitors. Three statistical methods were used to verify the performance of hDHODH PhSIA. Fischer's cross-validation test provided a 98% confidence leve

SUBMITTER: Shih KC 

PROVIDER: S-EPMC3913663 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature