Format

Send to

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

Natural product coumarins that inhibit human carbonic anhydrases.

Author information

1
Eskitis Institute, Griffith University, Nathan, Queensland 4111, Australia.

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.

PMID:
22892213
DOI:
10.1016/j.bmc.2012.07.021
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center