Abstract
A series of phenolic and saponin type natural products such as quercetin, rutin, catechin, epicatechin, silymarin, trojanoside H, astragaloside IV, astragaloside VIII and astrasieversianin X, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). We here report inhibitory effects of these compounds against five α-CA isozymes (hCA I, hCA II, bCA III, hCA IV and hCA VI). Most of the phenolic and saponin type compounds inhibited the isoenzymes quite effectively at low micromolar K(I)-s ranging between 0.1 and 4 µM, whereas a few derivatives were ineffective (K(I)-s > 100 µM). The results were remarkable which might lead to design of novel CAIs with a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Carbonic Anhydrases / isolation & purification
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Carbonic Anhydrases / metabolism*
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Dose-Response Relationship, Drug
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Humans
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Molecular Structure
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Phenols / chemical synthesis
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Phenols / chemistry
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Phenols / pharmacology*
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / isolation & purification
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Protein Isoforms / metabolism
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Saponins / chemical synthesis
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Saponins / chemistry
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Saponins / pharmacology*
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Structure-Activity Relationship
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
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Sulfonic Acids / chemistry
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Sulfonic Acids / pharmacology
Substances
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Carbonic Anhydrase Inhibitors
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Phenols
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Protein Isoforms
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Saponins
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Sulfonamides
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Sulfonic Acids
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Carbonic Anhydrases