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In silico approaches to demonstrate uzarigenin and calotropagenin as potential carbonic anhydrase II (CAII) inhibitors
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| Author:
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BASAVRAJ DEVARANAVADGI, VIKRAM PARTHASARATHY, ACHUTHAN RAGHAVA MENON
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| Abstract:
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ABSTRACT
Background
Inhibition studies on carbonic anhydrase II (CAII) (EC 4.2.1.1) activity are gaining attention due to their immense therapeutic application in the treatment of cancer, and obesity. Clinically used CAII inhibitors (CAIs), such as acetazolamide, and brinzolamide produce undesirable side effects like depression and nausea. So non-toxic and natural CAI is being researched with special interest. Previously, steroids such as bile acids, steroidal sulphamates, and sex hormones have been shown to inhibit CAII activity significantly. In the current in silico study, cardiotonic steroids (uzarigenine and calotropagenin) are being investigated as possible CAII inhibitors.
Objective
To evaluate uzarigenin and calotropagenin as potential inhibitors of carbonic anhydrase II (CAII) activity, using in silico methods
Methods and materials
Reverse pharmacophore screening and inverse docking of ligands were performed to identify potential targets. The results were validated by the docking study. The binding affinity and interactions of docked ligands viz, uzarigenin, calotropagenin, acetazolamide (standard) and cholic acid (positive control) with CAII macromolecule, were comparatively analyzed. MMPBSA calculation of protein-ligand complex was computed to determine the strength of binding. ADMET analysis was conducted to ascertain the drug-like properties of ligands.
Results and conclusion
Uzarigenin (Ki= -7.6 kcal/mol) and calotropagenin (Ki= -7.9 kcal/mol), by virtue of their interaction with catalytically important residues (Phe130, Ile91, Gln92), good fit score (2.82, and 2.93 respectively), and significant binding energy (?Ebind=-21.18 and -23.57kJ/mol respectively) in MMPBSA calculation can be further investigated as lead CAII inhibitors.
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| Keyword:
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Carbonic anhydrase II, cardenolides, reverse pharmacophore, uzarigenin, calotropogenin
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| EOI:
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| DOI:
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