4-[N-(substituted 4-pyrimidinyl)amino]benzenesulfonamides as inhibitors of carbonic anhydrase isozymes I, II, VII, and XIII.
A series of 4-[N-(substituted 4-pyrimidinyl)amino]benzenesulfonamides were designed and synthesised. Their binding potencies as inhibitors of selected recombinant human carbonic anhydrase (hCA) isozymes I, II, VII, and XIII were measured using isothermal titration calorimetry and the thermal shift assay. To determine the structural features of inhibitor binding, the crystal structures of several compounds in complex with hCA II were determined. Several compounds exhibited selectivity towards isozymes I, II, and XIII, and some were potent inhibitors of hCA VII.
Sūdžius
Jurgis
J
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, LT-03225 Vilnius, Lithuania.
Baranauskienė
Lina
L
Golovenko
Dmitrij
D
Matulienė
Jurgita
J
Michailovienė
Vilma
V
Torresan
Jolanta
J
Jachno
Jelena
J
Sukackaitė
Rasa
R
Manakova
Elena
E
Gražulis
Saulius
S
Tumkevičius
Sigitas
S
Matulis
Daumantas
D
D001665:Binding Sites; D002151:Calorimetry; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000096926:Benzenesulfonamides
D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D011743:Pyrimidines; D011994:Recombinant Proteins; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C483903:CA13 protein, human; C477051:carbonic anhydrase VI; C030986:pyrimidine