Molecular docking of pseudopeptidic imidazoles as selective inhibitors against CYP51 enzyme
Keywords:
molecular docking; CYP51; pseudopeptide imidazoles; selectivity coefficient.Abstract
P450 family, especially CYP51 protein, is a common target for the design of antifungal and antiprotozoal drugs. Designing new effective drugs against these pathogens is a necessity and a challenge for the scientific community. To this end, they are evaluated by molecular docking of five schemes of aryl-substituted imidazoles and pseudopeptic imidazoles against CYP51 proteins from different pathogens and against the similar human protein to estimate their selectivity. Once these calculations have been carried
out, none of the compounds studied appears to be an effective inhibitor against CYP51-L.infantum. However, for all the remaining proteins lower normalized coupling scores
are obtained, fundamentally for schemes 1 and 3. Given the geometry of the protein-linked complexes formed, schemes 2 and 4 appear to be more selective than schemes 1, 3 and 5. However, the highest estimated selectivity values are obtained for schemes 1 and 3 against CYP51-C.glabrata and for scheme 1 against CYP51-N.fowleri. In general, the direct relationship between the stability of the protein-ligated complex with the direct interaction of the ligand with the Fe2+ cation of the heme group, which provides
stability to the union.
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Copyright (c) 2024 Yonatan Mederos-Nuñez, Armando Ferrer-Serrano, Raidel Rosales-Rosabal, Rebeca Joa-Acree, América García-López
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