Selective inhibition of human carbonic anhydrases by novel amide derivatives of probenecid: Synthesis, biological evaluation and molecular modelling studies

Bioorganic & Medicinal Chemistry
2014.0

Abstract

Novel amide derivatives of probenecid, a well-known uricosuric agent, were synthesized and evaluated as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). The transmembrane isoforms (hCA IX and XII) were potently and selectively inhibited by some of them. The proposed chemical modification led to a complete loss of hCA II inhibition (K(i)s>10,000 nM) and enhanced the inhibitory activity against the tumour-associated hCA XII (compound 4 showed a K(i) value of 15.3 nM). The enzyme inhibitory data have also been validated by docking studies of the compounds within the active site of hCA XII.

Knowledge Graph

Similar Paper

Selective inhibition of human carbonic anhydrases by novel amide derivatives of probenecid: Synthesis, biological evaluation and molecular modelling studies
Bioorganic & Medicinal Chemistry 2014.0
New amide derivatives of Probenecid as selective inhibitors of carbonic anhydrase IX and XII: Biological evaluation and molecular modelling studies
Bioorganic & Medicinal Chemistry 2015.0
Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies
Bioorganic & Medicinal Chemistry 2015.0
Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII
European Journal of Medicinal Chemistry 2016.0
New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation
Bioorganic & Medicinal Chemistry 2020.0
Synthesis of a new series of N4-substituted 4-(2-aminoethyl)benzenesulfonamides and their inhibitory effect on human carbonic anhydrase cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII
European Journal of Medicinal Chemistry 2014.0
Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives
European Journal of Medicinal Chemistry 2011.0
Exploration of 2-phenylquinoline-4-carboxamide linked benzene sulfonamide derivatives as isoform selective inhibitors of transmembrane human carbonic anhydrases
European Journal of Medicinal Chemistry 2022.0
Isatin-pyrazole benzenesulfonamide hybrids potently inhibit tumor-associated carbonic anhydrase isoforms IX and XII
European Journal of Medicinal Chemistry 2015.0
Carbonic anhydrase inhibitors. Synthesis of a novel series of 5-substituted 2,4-dichlorobenzenesulfonamides and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII
European Journal of Medicinal Chemistry 2014.0