QSAR study on inhibition of brain 3-hydroxy-anthranilic acid dioxygenase (3-HAO): a molecular connectivity approach

The ability of 4,5-, 4,6-disubstituted and 4,5,6-trisubstituted 3-hydroxyanthranilic acid derivatives to reduce the production of the excitotoxin quinolinic acid (QUIN) by inhibition of brain 3-hydroxyanthranilic acid dioxygenase (3-HAO) has been investigated using molecular connectivity indices (0chi(v), 1chi(v), 2chi(v)). The in-vivo inhibition of 3-HAO in rat cortex (pIC(50), nM) is used for this purpose. The regression models obtained suggest that the degree of branching of the compounds under study have a dominant role in the observed inhibition potency. The data were used to generate quantitative structure-activity relationship (QSAR) models for estimating the potency of 3-HAO. The information obtained from the correlation should be useful in designing more potent analogues.