TY - JOUR
T1 - Nitric oxide inhibitory limonoids as potential anti-neuroinflammatory agents from Swietenia mahagoni
AU - Shi, Zhaoyu
AU - An, Lijun
AU - Yang, Xueyuan
AU - Xi, Yaru
AU - Zhang, Chenyue
AU - Shuo, Yuan
AU - Zhang, Jie
AU - Jin, Da Qing
AU - Ohizumi, Yasushi
AU - Lee, Dongho
AU - Xu, Jing
AU - Guo, Yuanqiang
PY - 2019/3
Y1 - 2019/3
N2 - Recent studies have revealed that there is a close relationship between neuroinflammation and Alzheimer's disease (AD) and compounds with anti-neuroinflammatory effects are potentially useful for the treatment of AD. A phytochemical investigation to obtain new neuroinflammatory inhibitors resulted in the isolation of four new and three known limonoids from Swietenia mahagoni. The structures of these limonoids were established by NMR, MS, and electronic circular dichroism (ECD) data analysis. Compounds 1–3 feature complicated polycyclic caged structures of limonoid orthoester and represent new examples of phragmalin-type limonoids. All of the isolates showed anti-neuroinflammatory activities by inhibiting nitric oxide (NO) release in LPS-induced murine microglial BV-2 cells with compounds 1 and 3–6 having IC 50 values of 26.8, 26.1, 26.0, 37.1, and 16.5 μM, respectively. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.
AB - Recent studies have revealed that there is a close relationship between neuroinflammation and Alzheimer's disease (AD) and compounds with anti-neuroinflammatory effects are potentially useful for the treatment of AD. A phytochemical investigation to obtain new neuroinflammatory inhibitors resulted in the isolation of four new and three known limonoids from Swietenia mahagoni. The structures of these limonoids were established by NMR, MS, and electronic circular dichroism (ECD) data analysis. Compounds 1–3 feature complicated polycyclic caged structures of limonoid orthoester and represent new examples of phragmalin-type limonoids. All of the isolates showed anti-neuroinflammatory activities by inhibiting nitric oxide (NO) release in LPS-induced murine microglial BV-2 cells with compounds 1 and 3–6 having IC 50 values of 26.8, 26.1, 26.0, 37.1, and 16.5 μM, respectively. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.
KW - Anti-neuroinflammatory
KW - Limonoids
KW - Molecular docking
KW - NO inhibitors
KW - Swietenia mahagoni
UR - http://www.scopus.com/inward/record.url?scp=85057223788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057223788&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2018.11.012
DO - 10.1016/j.bioorg.2018.11.012
M3 - Article
C2 - 30502629
AN - SCOPUS:85057223788
VL - 84
SP - 177
EP - 185
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
SN - 0045-2068
ER -