1,2,4-Thiadiazolidin-3,5-Diones as Inhibitors of Cysteine Proteases.

ABSTRACT: A focused library of 1,2,4-thiadiazolidin-3,5-diones (THIA-1-10), previously characterized as hydrogen sulfide (H₂S) donors, was evaluated for inhibitory activity against cysteine proteases. We included two key cysteine proteases aiming at antiviral drug development-SARS-CoV-2 3CLpro (Mpro) and PLpro-alongside reference enzymes Papain and Cathepsin L. The compounds exhibited distinct selectivity profiles and inhibition mechanisms. The ability to act as covalent inhibitors of 3CLpro in the nanomolar range is of particular interest, with compounds THIA-6, -7, and -10 proving to be the most potent inhibitors of the series, and compounds THIA-1, -2, and -8 proving to be the most selective with respect to the other proteases. We

SUBMITTER: Juliano MA 

PROVIDER: S-EPMC12526058 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature