Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties
Condensation of substituted anthranilic acids with 4-isothiocyanatoethyl-benzenesulfonamide led to series of heterocyclic benzenesulfonamides incorporating 2-mercapto-quinazolin-4-one tails. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isofor...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English English English |
| Published: |
Elsevier
2016
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/ http://irep.iium.edu.my/51705/1/2016_4100-4107.pdf http://irep.iium.edu.my/51705/4/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_Scopus.pdf http://irep.iium.edu.my/51705/5/51705_benzenesulfonamides%20with%20subnanomolar%20carbonic_WoS.pdf |
| Summary: | Condensation of substituted anthranilic acids with 4-isothiocyanatoethyl-benzenesulfonamide led to series
of heterocyclic benzenesulfonamides incorporating 2-mercapto-quinazolin-4-one tails. These sulfonamides
were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I
and II (cytosolic isozymes), as well as hCA XII (a transmembrane, tumor-associated enzyme also involved
in glaucoma-genesis). The new sulfonamides acted as medium potency inhibitors of hCA I (KIs of 28.5–
2954 nM), being highly effective as hCA II (KIs in the range of 0.62–12.4 nM) and XII (KIs of 0.54–
7.11 nM) inhibitors. All substitution patterns present in these compounds (e.g., halogens, methyl and
methoxy moieties, in positions 6, 7 and/or 8 of the 2-mercapto-quinazolin-4-one ring) led to highly effective
hCA II/XII inhibitors. These compounds should thus be of interest as preclinical candidates in
pathologies in which the activity of these enzymes should be inhibited, such as glaucoma (CA II and
XII as targets) or some tumors in which the activity of isoforms CA II and XII is dysregulated. |
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