Three-dimensional quantitative structure-activity relationship (QSAR) and receptor mapping of cytochrome P-450(14 alpha DM) inhibiting azole antifungal agents.
Molecular modeling was performed by a combined use of conformational analysis and 3D-QSAR methods to distinguish structural attributes common to a series of azole antifungal agents. Apex-3D program was used to recognize the common biophoric structural patterns of 13 diverse sets of azole antifungal compounds demonstrating different magnitudes of biological activity. Apex-3D identified three common biophoric features significant for activity: N1 atom of azole ring, the aromatic ring centroid 1, and aromatic ring centroid 2. A common biophore model proposed from the Apex-3D analysis can be useful for the design of novel cytochrome P-450(14 alpha DM) inhibiting antifungal agents.
Talele
T T
TT
Department of Chemical Technology, University of Mumbai, India.
Kulkarni
V M
VM
D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D065607:Cytochrome P-450 Enzyme Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D055672:Static Electricity; D058886:Sterol 14-Demethylase; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001393:Azoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase