Discovery of caffeic acid phenethyl ester derivatives as novel myeloid differentiation protein 2 inhibitors for treatment of acute lung injury.
作者： Lingfeng Chen , Yiyi Jin , Hongjin Chen , Chuchu Sun , Weitao Fu
DOI: 10.1016/J.EJMECH.2017.11.066
关键词:
摘要: Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes lipopolysaccharide (LPS), leading to initiation of inflammation through the activation Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester (CAPE) from propolis honeybee hives could interfere interactions between LPS and TLR4/MD2 complex, thereby has promising anti-inflammatory properties. In this study, we designed synthesized 48 CAPE derivatives evaluated their activities in mouse primary peritoneal macrophages (MPMs) activated by LPS. The most active compound, 10s, was found bind with MD2 high affinity, prevented formation LPS/MD2/TLR4 complex. binding mode 10s revealed that major were established via two key hydrogen bonds hydrophobic interactions. Furthermore, showed remarkable protective effects against LPS-caused ALI (acute lung injury) in vivo. Taken together, work provides new lead structures candidates as inhibitors for development drugs.
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