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Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Authors
Mishra, Chandra B.Tiwari, ManishaSupuran, Claudiu T.
Issue Date
Nov-2020
Publisher
WILEY
Keywords
arthritis; cancer; carbonic anhydrase; coumarin; epilepsy; glaucoma; inhibitor; neuropathic pain; obesity; selectivity; SLC-0111; sulfamate; sulfonamide
Citation
MEDICINAL RESEARCH REVIEWS, v.40, no.6, pp.2485 - 2565
Journal Title
MEDICINAL RESEARCH REVIEWS
Volume
40
Number
6
Start Page
2485
End Page
2565
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/2440
DOI
10.1002/med.21713
ISSN
0198-6325
Abstract
Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H+ ions and play a crucial role in regulating many physiological processes. CAs are well-studied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.
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