N-methoxy-β-carboline alkaloids with inhibitory activities against Aβ42 aggregation and acetylcholinesterase from the stems of Picrasma quassioides

Jie Zhang; Sen-Sen Zhao; Jun Xie; Jian Yang; Guo-Dong Chen; Dan Hu; Wei-Guang Zhang; Chuan-Xi Wang; Xin-Sheng Yao; Hao Gao

doi:10.1016/j.bioorg.2020.104043

N-methoxy-β-carboline alkaloids with inhibitory activities against Aβ₄₂ aggregation and acetylcholinesterase from the stems of Picrasma quassioides

Bioorg Chem. 2020 Aug:101:104043. doi: 10.1016/j.bioorg.2020.104043. Epub 2020 Jun 25.

Authors

Jie Zhang¹, Sen-Sen Zhao², Jun Xie², Jian Yang³, Guo-Dong Chen², Dan Hu², Wei-Guang Zhang⁴, Chuan-Xi Wang⁵, Xin-Sheng Yao¹, Hao Gao⁶

Affiliations

¹ Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, People's Republic of China; College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
² Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, People's Republic of China.
³ College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
⁴ School of Chemistry and Environment, South China Normal University, Guangzhou 510006, People's Republic of China.
⁵ Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, People's Republic of China. Electronic address: tcxwang@jnu.edu.cn.
⁶ Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, People's Republic of China; College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: tghao@jnu.edu.cn.

PMID: 32629286
DOI: 10.1016/j.bioorg.2020.104043

Abstract

Nine new N-methoxy-β-carboline alkaloids (NMCAs) (1a/1b-3a/3b and 4-6) and two known NMCAs (7 and 8) were isolated from the stems of Picrasma quassioides. Their structures were elucidated by spectroscopic data analyses, quantum chemical calculations, and single-crystal X-ray crystallographic data. An analysis of the ¹³C NMR chemical shifts of the N-methoxy groups in these NMCAs and 41 gathered known compounds reveals the phenomenon that the chemical shifts of all these N-methoxy groups are greater than δ_C 62, which can be used to recognize the N-methoxy group rapidly. In addition, the acetylcholinesterase (AChE) and Aβ₄₂ aggregation inhibitory activities of 1-8 were evaluated. Compounds 1, 2, 7, and 8 displayed AChE inhibitory activity with IC₅₀ values of 14.9, 13.2, 17.6, and 43.9 μM, respectively. Compound 2 showed inhibition activity against Aβ₄₂ aggregation with an IC₅₀ value of 10.1 μM.

Keywords: AChE inhibitory activity; Aβ(42) aggregation inhibitory activity; N-Methoxy-β-carboline alkaloids; Picrasma quassioides.

Publication types

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

MeSH terms

Acetylcholinesterase
Alkaloids / chemistry*
Amyloid beta-Peptides / drug effects*
Humans
Molecular Structure
Peptide Fragments / drug effects*
Picrasma / chemistry*
Structure-Activity Relationship

Substances

Alkaloids
Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (1-42)
Acetylcholinesterase