Structure-based lead optimization to improve the antifungal potency of the tetrahydroimidazo pyridine inhibitors targeted to Candida albicans dihydrofolate reductase and lanosterol 14-alpha-demethylase
| Autor: | Srimai Vuppala, Ramesh Kumar Chitumalla, Bo Sun Joo, Joonkyung Jang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
biology
Chemistry Stereochemistry Lanosterol Organic Chemistry biology.organism_classification chemistry.chemical_compound Docking (molecular) Dihydrofolate reductase Lanosterol 14 alpha-demethylase Lipinski's rule of five biology.protein Potency General Pharmacology Toxicology and Pharmaceutics Pharmacophore Candida albicans |
| Zdroj: | Medicinal Chemistry Research. 28:1674-1682 |
| ISSN: | 1554-8120 1054-2523 |
| Popis: | We investigate the binding and inhibition profiles for a selected dataset of tetrahydroimidazo pyridine molecules against Candida albicans dihydrofolate reductase (DHFR) and lanosterol 14-alpha-demethylase (CYP51). A hit molecule was screened and identified through Lipinski’s rule of five, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and the molecular docking. Some inhibitors of our design have shown positive drug scores, good solubilities, and high docking scores over the selected dataset. The first-principles calculation based on the density functional theory was carried out to understand how the electronic distributions of frontier orbitals of molecules affect their inhibition profiles. The present structure-based approach enabled us to design new pharmacophore analogs with improved ADMET profile, drug scores, and docking scores against selected receptors. |
| Databáze: | OpenAIRE |
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