Alopecines A-E, five chloro-containing matrine-type alkaloids with immunosuppressive activities from the seeds of Sophora alopecuroides

Xiao-Feng Wang; Zhengdan Zhu; Ting-Ting Hao; Qiang-Qiang Fang; Kun Jiang; Shi-Jin Qu; Jiang-Pin Zuo; Weiliang Zhu; Shi-Jun He; Chang-Heng Tan

doi:10.1016/j.bioorg.2020.103812

Alopecines A-E, five chloro-containing matrine-type alkaloids with immunosuppressive activities from the seeds of Sophora alopecuroides

Bioorg Chem. 2020 Jun:99:103812. doi: 10.1016/j.bioorg.2020.103812. Epub 2020 Apr 9.

Authors

Affiliations

¹ Department of Natural Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
² CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
³ Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
⁴ Department of Natural Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁵ Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
⁶ Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: heshijun@simm.ac.cn.
⁷ Department of Natural Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: chtan@simm.ac.cn.

PMID: 32302796
DOI: 10.1016/j.bioorg.2020.103812

Abstract

Alopecines A-E (1-5), five unusual matrine-type alkaloids featuring with an additional dichlorocyclopropane (1-3) or a di/tri-chloromethyl (4/5) attached on the D ring, were isolated from the seeds of Sophora alopecuroides. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques, and X-ray diffraction analyses or time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Alkaloid 4 exhibited potent inhibitory effects on the proliferation of ConA-induced T lymphocytes or LPS-induced B cells with IC₅₀ value of 3.98 or 3.74 μM, respectively.

Keywords: Absolute configuration; Alkaloids; Cl-containing matrines; Immunosuppressive activity; Sophora alopecuroides.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkaloids / chemistry
Alkaloids / isolation & purification
Alkaloids / pharmacology*
Animals
B-Lymphocytes / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Cells, Cultured
Concanavalin A / antagonists & inhibitors
Concanavalin A / pharmacology
Dose-Response Relationship, Drug
Female
Immunosuppressive Agents / chemistry
Immunosuppressive Agents / isolation & purification
Immunosuppressive Agents / pharmacology*
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Mice
Mice, Inbred BALB C
Molecular Conformation
Plant Extracts / chemistry
Plant Extracts / isolation & purification
Plant Extracts / pharmacology*
Seeds / chemistry
Sophora / chemistry*
Stereoisomerism
Structure-Activity Relationship
T-Lymphocytes / drug effects

Substances

Alkaloids
Immunosuppressive Agents
Lipopolysaccharides
Plant Extracts
Concanavalin A