The antibiotic furagin and its derivatives are isoform-selective human carbonic anhydrase inhibitors.

ABSTRACT: The clinically used antibiotic Furagin and its derivatives possess inhibitory activity on human (h) carbonic anhydrases (CA, EC 4.2.1.1), some of which are highly expressed in various tissues and malignancies (hCA IX/XII). Furagin exhibited good hCA IX and XII inhibition with K_Is of 260 and 57 nM, respectively. It does not inhibit off-target CA I and poorly inhibited CA II (K_I = 9.6 μM). Some synthesised Furagin derivatives with aminohydantoin moieties as zinc binding group exhibited weak inhibition of CA I/II, and good inhibition of CA IX/XII with K_Is ranging from 350 to 7400 and 150 to 5600 nM, respectively. Docking and molecular dynamics simulations suggest that selectivity for the cancer-associated CA IX/XII over CA II is due to str

SUBMITTER: Pustenko A 

PROVIDER: S-EPMC7178874 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature