Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 23, Issue 24, Pages 7751-7764Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2015.11.023
Keywords
Carbonic anhydrase; Sulfonamide; Quinazoline; Tail approach
Funding
- National Plan of Science, Technology and Innovation, King Saud University, Riyadh, Saudi Arabia [11-MED-1874-2]
- European Union
Ask authors/readers for more resources
Three series of sulfonamides incorporating long, bulky tails were obtained by applying synthetic strategies in which substituted anthranilic acids, quinazolines and aromatic sulfonamides have been used as starting materials. They incorporate long, bulky diamide-, 4-oxoquinazoline-3-yl-or quinazoline-4-yl moieties in their molecules, and were investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides showed excellent inhibitory effects against the four isoforms, with K(I)s of 7.6-322 nM against hCA I, of 0.06-85.4 nM against hCA II; of 6.7-152 nM against hCA IX and of 0.49-237 nM against hCA XII; respectively. However no relevant isoform-selective behavior has been observed for any of them, although hCA II and XII, isoforms involved in glaucoma-genesis were the most inhibited ones. The structure-activity relationship for inhibiting the four CAs with these derivatives is discussed in detail. (c) 2015 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available