Abstract:
:A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50-50.5nM), hCA IX (KIs of 1.8-228.5nM), and hCA XII (KIs of 3.5-96.2nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure-activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Angapelly S,Ramya PVS,Angeli A,Del Prete S,Capasso C,Arifuddin M,Supuran CTdoi
10.1016/j.bmc.2017.08.047subject
Has Abstractpub_date
2017-10-15 00:00:00pages
5726-5732issue
20eissn
0968-0896issn
1464-3391pii
S0968-0896(17)31520-1journal_volume
25pub_type
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