Journal Article

PUBDB-2020-03220

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Halogenated and di-substituted benzenesulfonamides as selective inhibitors of carbonic anhydrase isoforms

Zakšauskas, A. ; Čapkauskaitė, E. ; Jezepčikas, L. ; Linkuvienė, V. ; Paketurytė, V. ; Smirnov, A. ; Leitans, J. ; Kazaks, A. ; Dvinskis, E. ; Manakova, E. ; Gražulis, S. ; Tars, K. ; Matulis, D. (Corresponding author)

2020
Elsevier10887 Amsterdam [u.a.]

This record in other databases:      

Please use a persistent id in citations: doi:10.1016/j.ejmech.2019.111825

Abstract: By applying an approach of a “ring with two tails”, a series of novel inhibitors possessing high-affinity and significant selectivity towards selected carbonic anhydrase (CA) isoforms has been designed. The “ring” consists of 2-chloro/bromo-benzenesulfonamide, where the sulfonamide group is as an anchor coordinating the Zn(II) in the active site of CAs, and halogen atom orients the ring affecting the affinity and selectivity. First “tail” is a substituent containing carbonyl, carboxyl, hydroxyl, ether groups or hydrophilic amide linkage. The second “tail” contains aryl- or alkyl-substituents attached through a sulfanyl or sulfonyl group. Both “tails” are connected to the benzene ring and play a crucial role in selectivity. Varying the substituents, we designed compounds selective for CA VII, CA IX, CA XII, or CA XIV.Since due to binding-linked protonation reactions the binding-ready fractions of the compound and protein are much lower than one, the “intrinsic” affinities were calculated that should be used to study correlations between crystal structures and the thermodynamics of binding for rational drug design. The “intrinsic” affinities together with the intrinsic enthalpies and entropies of binding together with co-crystal structures were used demonstrate structural factors determining major contributions for compound affinity and selectivity.

---

Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (POF3-622) (POF3-622)

Experiment(s):

1. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2020

---

Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---