(R)-/(S)-10-camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases.
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Maresca A, Supuran CT
(R)-/(S)-10-camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases.
Bioorg Med Chem Lett. 2011 Mar 1;21(5):1334-7. doi: 10.1016/j.bmcl.2011.01.050. Epub 2011 Jan 18.
- PubMed ID
- 21300547 [ View in PubMed]
- Abstract
A series of aromatic and heterocyclic sulfonamides incorporating R- and S-camphorsulfonyl moieties were synthesized and investigated for the inhibition of several mammalian isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The new sulfonamides selectively inhibited the mitochondrial isozymes hCA VA and VB (h=human isoform) over the cytosolic, off-target ones hCA I and II, with inhibition constants in the low nanomolar range. The chirality and position of the groups substituting the sulfonamide scaffold greatly influenced CA inhibitory properties. These compounds are excellent leads for designing isoform-selective enzyme inhibitors targeting mitochondrial CAs involved in lipogenesis and obesity.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Diclofenamide Carbonic anhydrase 1 Ki (nM) 1200 N/A N/A Details Diclofenamide Carbonic anhydrase 2 Ki (nM) 38 N/A N/A Details Ethoxzolamide Carbonic anhydrase 1 Ki (nM) 25 N/A N/A Details Ethoxzolamide Carbonic anhydrase 2 Ki (nM) 8 N/A N/A Details Topiramate Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 10 N/A N/A Details Zonisamide Carbonic anhydrase 1 Ki (nM) 56 N/A N/A Details Zonisamide Carbonic anhydrase 2 Ki (nM) 35 N/A N/A Details Zonisamide Carbonic anhydrase 5A, mitochondrial Ki (nM) 20 N/A N/A Details Zonisamide Carbonic anhydrase 5B, mitochondrial Ki (nM) 6033 N/A N/A Details