Identification of Important Chemical Features of 11β-Hydroxysteroid Dehydrogenase Type1 Inhibitors: Application of Ligand Based Virtual Screening and Density Functional Theory

Autor: Young-sik Sohn, Keun Woo Lee, C. Meganathan, Sundaraganesan Namadevan, Sugunadevi Sakkiah
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Models
Molecular
Quantitative structure–activity relationship
Hydrocortisone
Quantitative Structure-Activity Relationship
Computational biology
Molecular Docking Simulation
Article
Catalysis
Inorganic Chemistry
lcsh:Chemistry
11-beta-Hydroxysteroid Dehydrogenase Type 1
Humans
Physical and Theoretical Chemistry
density function theory
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Virtual screening
Binding Sites
pharmacophore
diabetes
Chemistry
Organic Chemistry
General Medicine
11β-hydroxysteroid dehydrogenase
molecular docking
11 beta-hydroxysteroid dehydrogenase
density functiontheory
virtual screening
Ligand (biochemistry)
Computer Science Applications
Cortisone
Glucose
Diabetes Mellitus
Type 2
Biochemistry
lcsh:Biology (General)
lcsh:QD1-999
Drug Design
Lipinski's rule of five
Insulin Resistance
Pharmacophore
Decoy
Chemical database
hormones
hormone substitutes
and hormone antagonists
Zdroj: International Journal of Molecular Sciences, Vol 13, Iss 4, Pp 5138-5162 (2012)
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(13): 4
International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 13; Issue 4; Pages: 5138-5162
ISSN: 1422-0067
Popis: 11 beta-Hydroxysteroid dehydrogenase type1 (11 beta HSD1) regulates the conversion from inactive cortisone to active cortisol. Increased cortisol results in diabetes, hence quelling the activity of 11 beta HSD1 has been thought of as an effective approach for the treatment of diabetes. Quantitative hypotheses were developed and validated to identify the critical chemical features with reliable geometric constraints that contribute to the inhibition of 11 beta HSD1 function. The best hypothesis, Hypo1, which contains one-HBA; one-Hy-Ali, and two-RA features, was validated using Fischer's randomization method, a test and a decoy set. The well validated, Hypo1, was used as 3D query to perform a virtual screening of three different chemical databases. Compounds selected by Hypo1 in the virtual screening were filtered by applying Lipinski's rule of five, ADMET, and molecular docking. Finally, five hit compounds were selected as virtual novel hit molecules for 11 beta HSD1 based on their electronic properties calculated by Density functional theory.
Databáze: OpenAIRE
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