Natural product coumarins that inhibit human carbonic anhydrases.

Article Details

Citation
Copy to clipboard

Davis RA, Vullo D, Maresca A, Supuran CT, Poulsen SA

Natural product coumarins that inhibit human carbonic anhydrases.

Bioorg Med Chem. 2013 Mar 15;21(6):1539-43. doi: 10.1016/j.bmc.2012.07.021. Epub 2012 Jul 23.

PubMed ID
22892213 [ View in PubMed
]
Abstract

Natural products (NPs) have proven to be an invaluable source of new chemotherapies yet very few have been explored to source small molecule carbonic anhydrase (CA) inhibitors. CA enzymes underpin physiological pH and are critical to the progression of several diseases including cancer. The present study is the first to more widely investigate NP coumarins for CA inhibition following the recent discovery of a NP coumarin CA inhibitor. We assembled a NP library comprising 24 plant coumarins (compounds 4-27) and three ascidian coumarins (compounds 28-30) that together provide a diverse collection of structures containing the coumarin pharmacophore. This library was then evaluated for inhibition of six human CA isozymes (CAs I, II, VII, IX, XII and XIII) and a broad range of inhibition and isozyme selectivity profiles were evident. Our findings provide a platform to support further evaluation of NPs for the discovery of new chemotypes that inhibit disease relevant CA enzymes.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Ellagic acidCarbonic anhydrase 1Ki (nM)68200N/AN/ADetails
Ellagic acidCarbonic anhydrase 12Ki (nM)8150N/AN/ADetails
Ellagic acidCarbonic anhydrase 2Ki (nM)>100000N/AN/ADetails
Ellagic acidCarbonic anhydrase 7Ki (nM)8790N/AN/ADetails
Ellagic acidCarbonic anhydrase 9Ki (nM)79800N/AN/ADetails