Carbonic anhydrase inhibitors: two-prong versus mono-prong inhibitors of isoforms I, II, IX, and XII exemplified by photochromic cis-1,2-alpha-dithienylethene derivatives.
We investigated the inhibition of five physiologically relevant CA isoforms with photochromic cis-1,2-alpha-dithienylethene-based compounds incorporating either a benzenesulfonamide and Cu(II)-iminodiacetic acid (IDA)-, bis-benzenesulfonamide-, bis-Cu(II)-IDA-, and bis-ethyleneglycol-methyl ether moieties, in both their open- and closed-ring forms. For hCA I the best inhibitors were the mono-prong bis-sulfonamide and the bis-Cu-IDA complexes (K(I)s of 2-3 nM) in their open form. For hCA II, best inhibitors were the open and closed forms of the mono-prong bis-sulfonamide (K(I)s of 13-18 nM). hCA IX was moderately inhibited by these compounds (K(I)s of 9-376 nM) whereas hCA XII and XIV were less susceptible to inhibition (K(I)s of 1.12-16.7 microM).
Vomasta
Daniel
D
Institute of Organic Chemistry, University of Regensburg, 93040 Regensburg, Germany.
Innocenti
Alessio
A
König
Burkhard
B
Supuran
Claudiu T
CT
D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000737:chemistry; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D010777:Photochemistry / Q000379:methods*; D013329:Structure-Activity Relationship
D000951:Antigens, Neoplasm; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII