TY - JOUR

T1 - Screening of benzenesulfonamide in combination with chemically diverse fragments against carbonic anhydrase by differential scanning fluorimetry

AU - Krasavin, Mikhail

AU - Kalinin, Stanislav

AU - Zozulya, Sergey

AU - Gryniukova, Anastasiia

AU - Borysko, Petro

AU - Angeli, Andrea

AU - Supuran, Claudiu T.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - The differential scanning fluorimetry (DSF) screening of 5.692 fragments in combination with benzenesulfonamide (BSA) against bovine carbonic anhydrase (bCA) delivered >100 hits that either caused, on their own, a significant thermal shift (ΔTm, °C) in the protein melting temperature or significantly influenced the thermal shift observed for BSA alone. Three hits based on 1,2,3-triazole moiety represent the periphery of the recently reported potent inhibitors of hCA II, IX and XII which were efficacious in vivo. Such a re-discovery of suitable BSA periphery essentially validates the new fragment-based approach to the discovery of future CAIs. Structures of other validated fragment hits are reported.

AB - The differential scanning fluorimetry (DSF) screening of 5.692 fragments in combination with benzenesulfonamide (BSA) against bovine carbonic anhydrase (bCA) delivered >100 hits that either caused, on their own, a significant thermal shift (ΔTm, °C) in the protein melting temperature or significantly influenced the thermal shift observed for BSA alone. Three hits based on 1,2,3-triazole moiety represent the periphery of the recently reported potent inhibitors of hCA II, IX and XII which were efficacious in vivo. Such a re-discovery of suitable BSA periphery essentially validates the new fragment-based approach to the discovery of future CAIs. Structures of other validated fragment hits are reported.

KW - carbonic anhydrase II

KW - Differential scanning fluorimetry

KW - fragment-based drug discovery

KW - primary sulphonamide

KW - protein affinity

KW - thermal shift assay

KW - zinc binding group

KW - Humans

KW - Fluorometry

KW - Carbonic Anhydrase IX/antagonists & inhibitors

KW - Carbonic Anhydrase Inhibitors/chemical synthesis

KW - Carbonic Anhydrases/metabolism

KW - Molecular Structure

KW - Sulfonamides/chemical synthesis

KW - Carbonic Anhydrase II/antagonists & inhibitors

KW - Drug Evaluation, Preclinical

KW - DESIGN

KW - STABILITY

KW - IDENTIFICATION

KW - IX

KW - POTENT

KW - INHIBITORS

KW - BINDING

UR - http://www.scopus.com/inward/record.url?scp=85075913695&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/99de8f64-f4e2-3267-9c05-dfc854b20bf0/

U2 - 10.1080/14756366.2019.1698562

DO - 10.1080/14756366.2019.1698562

M3 - Article

C2 - 31797704

AN - SCOPUS:85075913695

VL - 35

SP - 306

EP - 310

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

IS - 1

ER -