TY  - JOUR
AU  - Čapkauskaitė, Edita
AU  - Zubrienė, Asta
AU  - Smirnov, Alexey
AU  - Torresan, Jolanta
AU  - Kišonaitė, Miglė
AU  - Kazokaitė, Justina
AU  - Gylytė, Joana
AU  - Michailovienė, Vilma
AU  - Jogaitė, Vaida
AU  - Manakova, Elena
AU  - Gražulis, Saulius
AU  - Tumkevičius, Sigitas
AU  - Matulis, Daumantas
TI  - Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic anhydrases I, II, VI, VII, XII, and XIII
JO  - Bioorganic & medicinal chemistry
VL  - 21
IS  - 22
SN  - 0968-0896
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DESY-2014-01386
SP  - 6937 - 6947
PY  - 2013
N1  - © Elsevier Ltd. ; Post referee fulltext in progress; Embargo 12 months from publication
AB  - Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzenesulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000325759800009
C6  - pmid:24103428
DO  - DOI:10.1016/j.bmc.2013.09.029
UR  - https://bib-pubdb1.desy.de/record/166504
ER  -