Development of (4-Phenylamino)quinazoline Alkylthiourea Derivatives as Novel NF-κB Inhibitors.

ABSTRACT: For many inflammatory diseases, new effective drugs with fewer side effects are needed. While it appears promising to target the activation of the central pro-inflammatory transcription factor NF-κB, many previously discovered agents suffered from cytotoxicity. In this study, new alkylthiourea quinazoline derivatives were developed that selectively inhibit the activation of NF-κB in macrophage-like THP-1 cells while showing low general cytotoxicity. One of the best compounds, 19, strongly inhibited the production of IL-6 (IC₅₀ = 0.84 µM) and, less potently, of TNFα (IC₅₀ = 4.0 µM); in comparison, the reference compound, caffeic acid phenethyl ester (CAPE), showed IC₅₀s of 1.1 and 11.4 µM, respectively. Interestingly, 19 was found to block the

SUBMITTER: Darwish SS 

PROVIDER: S-EPMC9322122 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature