Abstract
A small collection of 26 structurally novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group, were synthesised and tested in enzyme inhibition assays against the tumour-associated hCA IX enzyme. Inhibition constants in the lower micromolar region (KI < 25 μM) have been measured for 17 of the 26 compounds. Even though the KI values are relatively weak, the fact that they do not contain a sulphonamide moiety suggests that these compounds do not interact with the active site zinc ion. Therefore, docking studies and molecular dynamics simulations have been performed to suggest binding poses for these structurally novel inhibitors.
Keywords:
carbonic anhydrase IX; docking; hCA IX; molecular modelling; thiazolidinone.
MeSH terms
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / metabolism
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Carbonic Anhydrase IX / antagonists & inhibitors*
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Carbonic Anhydrase IX / chemistry
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Carbonic Anhydrase IX / metabolism
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Carbonic Anhydrase Inhibitors / chemical synthesis
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Carbonic Anhydrase Inhibitors / chemistry*
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Carbonic Anhydrase Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Humans
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Molecular Dynamics Simulation
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Molecular Structure
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Organometallic Compounds / chemistry
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Organometallic Compounds / pharmacology
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Structure-Activity Relationship
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Sulfanilamide
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Sulfanilamides / chemistry
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Sulfanilamides / pharmacology
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Thiazolidines / chemical synthesis
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Thiazolidines / chemistry*
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Thiazolidines / pharmacology*
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Zinc / chemistry
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Zinc / pharmacology
Substances
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Antigens, Neoplasm
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Carbonic Anhydrase Inhibitors
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Organometallic Compounds
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Sulfanilamides
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Thiazolidines
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Sulfanilamide
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CA9 protein, human
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Carbonic Anhydrase IX
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Zinc