Exploring novel isatin derivatives as SARS-CoV-2 3CL^pro inhibitors.

Authors

Jian Song, Cai Shi, Boning Yang, Jingxiang Yang, Caifei Huang, Jiaqi Liu, Shuwen Wu, Shuyuan Mo, Jian Yang

Published in

Journal of enzyme inhibition and medicinal chemistry. Volume 41. Issue 1. Pages 2707859. Epub Sep 10, 2026.

Abstract

A series of novel isatin derivatives were synthesised by incorporating phenyl, biphenyl, naphthyl and indolyl moieties into the N-1 position and screened in vitro against SARS-CoV-2 3CL^pro, respectively. These isatin compounds with halogen substitution at the isatin ring and trifluoromethylbenzyl substitution at N-1 position were strong inhibitors of SARS-CoV-2 3CL^pro. Furthermore, introduction of electron withdrawing groups at the C-5 and C-7 of isatin ring, such as bromo group, might be more favourable for the inhibition activity. The most potent compound 34 demonstrated an IC₅₀ of 0.363 ± 0.045 µM against SARS-CoV-2 3CL^pro. Additionally, a jump dilution assay, surface plasmon resonance (SPR) spectroscopy and in silico analysis were used to measure the binding of compound 34 to SARS-CoV-2 3CL^pro respectively, supporting the obtained in vitro findings. Moreover, compound 34 inhibited viral cell proliferation with an IC₅₀ of 0.404 ± 0.021 μM (selectivity index (SI) =170). Therefore, it is worth to further investigate compound 34 as a SARS-CoV-2 3CL^pro inhibitor.

PMID:
42723354
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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