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.
Agrawal
V K
VK
Computer & QSAR Laboratories, A. P. S. University, Rewa-486 003, India. vijay-agrawal@lycos.com
Sohgaura
R
R
Khadikar
P V
PV
D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000818:Animals; D001921:Brain / Q000201:enzymology*; D049308:Dioxygenases; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D012044:Regression Analysis
D004791:Enzyme Inhibitors; D010105:Oxygenases; D049308:Dioxygenases; D050561:3-Hydroxyanthranilate 3,4-Dioxygenase