VIRTUAL SCREENING OF TRIAZOLES INIBITORS OF BETA HDROXYSTEROID DESHYDROGENASE ENZYME USING - ADME - MOLECULAR DOCKING, AND MOLECULAR DYNAMICS SIMULATION STUDIES
DOI:
https://doi.org/10.4314/jfas.v12i2.13Keywords:
11 β -HSD1-11 β –HSD2– Hypertensio –1,2,4-Triazoles- Bioactivity Properties(Molecular Operating Environment)Abstract
Hypertension, or elevated arterial blood pressure, is a substantial public health problem. The two 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes catalyze the interconversion of cortisol and cortisone. Inhibition of two 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes present the key in the disease of arterial hypertension 1(PAH) treatment actually an important number of synthetics inhibitors of this enzyme were studied. However Triazoles synthetic inhibitors were identified as the most efficient ones, indeed, the most commercialized treatment of arterial hypertension 1 is Triazoles. The research and synthesis of new pharmacologically active molecules is the subject of a theoretical study by molecular modeling. Our research consists in studying the inhibition of the enzymes applied in the disease of arterial hypertension 11-beta-hydroxysteroid dehydrogenase of type 1 and type 2 with some derivatives of 1,2,4-triazoles by means of molecular docking and molecular dynamics approaches. Theoretical calculation was done using a MOE program for molecular docking and HyperChem and others softwares were used to find the best compounds with high affinity. The interactions between the studied inhibitors and our target were further explored through molecular docking and molecular dynamics simulations, in the presence of water molecules. The molecular dynamics study was done for the best derivatives of 1,2,4-triazoles inhibitors (deducted from the docking best scores for L2 and L1, and lowest score for Lref). A few key residues ( N-14 with oxygen receptor interaction H- donor) at the binding site of 11-beta-hydroxysteroid dehydrogenase of type 1 (11β-HSD1) and type2 (11β-HSD2) were identified. Obtained Docking and molecular dynamics result, both leads to the same conclusion and predict that L2 subsisted derivatives of 1, 2, 4-triazoles is the best inhibitor candidate.
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