Target-specific anti-fungal discovery by targeting Geotrichum candidum histidinol dehydrogenase: a hybrid approach.
This study describes a hybrid approach of screening substrate analogue inhibitors of histidinol dehydrogenase. Imidazole derivative library of approximately 400 compounds classified using Hierarchical cluster analysis, representative compounds of each class were tested in enzymatic assay and used for the development of quantitative structure-activity relationship models. Rest of the compounds in the library were screened using developed models and compounds predicted active were retested. 60% of the predicted compounds showed enzyme inhibition activity with IC(50) values ranged between 5.2 and 58.0 microm range and have fungistatic activity.
Pahwa
Sonia
S
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector, Punjab, India.
Chavan
Archana G
AG
Jain
Rahul
R
Roy
Nilanjan
N
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000465:Algorithms; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D005848:Geotrichum / Q000187:drug effects / Q000201:enzymology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship
D000935:Antifungal Agents; D007093:Imidazoles; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase