European Journal of Medicinal Chemistry p. 253 - 266 (2018)
Update date:2022-08-15
Topics:
Xu, Yao
Chen, Shujun
Cao, Ying
Zhou, Pingzheng
Chen, Zhipeng
Cheng, Kui
Toll-like receptor 4 (TLR4) initiates innate immune response to release inflammatory cytokines and has been pathologically linked to variety of inflammatory diseases. Recently, we found that Carvedilol, as the classic anti-heart failure and anti-inflammatory clinic drug, could inhibit the TLR4 signaling in the TLR4 overexpressed cells. Herein, we have designed and synthesized a small library of novel Carvedilol derivatives and investigated their potential inhibitory activity. The results indicate that the most potent compound 8a (SMU-XY3) could effectively inhibited TLR4 protein and the LPS triggered alkaline phosphatase signaling in HEK-Blue hTLR4 cells. It down regulated the nitric oxide (NO) in both RAW264.7 cells and BV-2 microglial cells, in addition to blocking the TNF-α signaling in ex-vivo human peripheral blood mononuclear cells (PBMC). More interestingly, 8a shows higher affinity to hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) over HCN2, which probably indicates the new application of TLR4 inhibitor 8a in heart failure, coronary heart disease, and other inflammatory diseases.
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Doi:10.1021/ol061086p
(2006)Doi:10.1016/0022-328X(84)80080-7
(1984)Doi:10.1002/ejoc.200600119
(2006)Doi:10.1002/adsc.200505162
(2005)Doi:10.1021/jo401867e
(2013)Doi:10.1055/s-2006-942373
(2006)