%0 Journal Article
%T Discovery of novel oridonin sulfamide derivatives as potent NLRP3 inhibitors by a visible-light photocatalysis-enabled peripheral editing.
%A Li M
%A Wang C
%A Ye S
%A Li W
%A Zhang Y
%A Yan J
%A Wang Y
%A Yang H
%A Wu Y
%A Zhang Y
%A Zhang H
%A Miao Z
%J Bioorg Med Chem Lett
%V 99
%N 0
%D 2024 Feb 1
%M 38244941
%F 2.94
%R 10.1016/j.bmcl.2024.129621
%X The progress of organicsyntheticmethod can promote late-stage lead compound modification and novel active compound discovery. Molecular editing technology in the field of organic synthesis, including peripheral and skeletal editing, facilitates rapid access to molecular diversity of a lead compound. Peripheral editing of CH bond activation is gradually used in lead optimization to afford novel active scaffolds and chemical space exploitation. To develop oridonin derivatives with high anti-inflammatory potency, novel oridonin sulfamides had been designed and synthesized by a scaffoldhopping strategy based on a visible-light photocatalysis peripheral editing. All novel compounds revealed measurable inhibition of IL-1β and low cytotoxicity in THP-1 cells. The docking study indicated that the best active compound ZM640 was accommodated in thebinding site of NLRP3 with two hydrogen bond interaction. These preliminary results confirm that α, β-unsaturated carbonyl of oridonin is not essential for NLRP3 inhibitory effect. This new oridonin scaffold has its potential to be further developed as a promising class of NLRP3 inhibitors.