N -Methyl Costaricine and Costaricine, Two Potent Butyrylcholinesterase Inhibitors from Alseodaphne pendulifolia Gamb

• Published in: International journal of molecular sciences 2023-06, Vol.24 (13), p.10699
• Main Authors: Husna Hasnan, Muhammad Hafiz, Sivasothy, Yasodha, Khaw, Kooi Yeong, Nafiah, Mohd Azlan, Hazni, Hazrina, Litaudon, Marc, Wan Ruzali, Wan Adriyani, Liew, Sook Yee, Awang, Khalijah
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; Alkaloids; Alkaloids - chemistry; Alkaloids - pharmacology; Alzheimer's disease; Benzylisoquinolines; Butyrylcholinesterase - metabolism; Chemical Sciences; Cholinesterase; Cholinesterase inhibitors; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Cholinesterase Inhibitors - therapeutic use; Column chromatography; Communication; Dichloromethane; Drug development; Drugs; Galantamine; Inhibitors; Lauraceae - chemistry; Lead compounds; Metabolites; Nitrogen; Plant Extracts - chemistry; Plant Extracts - pharmacology; Secondary metabolites; Thin layer chromatography; Two dimensional analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241310699

Studies have been conducted over the last decade to identify secondary metabolites from plants, in particular those from the class of alkaloids, for the development of new anti-Alzheimer's disease (AD) drugs. The genus , comprising a wide range of alkaloids, is a promising source for the discovery of new cholinesterase inhibitors, the first-line treatment for AD. With regard to this, a phytochemical investigation of the dichloromethane extract of the bark of Gamb. was conducted. Repeated column chromatography and preparative thin-layer chromatography led to the isolation of a new bisbenzylisoquinoline alkaloid, -methyl costaricine ( ), together with costaricine ( ), hernagine ( ), -methyl hernagine ( ), corydine ( ), and oxohernagine ( ). Their structures were elucidated by the 1D- and 2D-NMR techniques and LCMS-IT-TOF analysis. Compounds and were more-potent BChE inhibitors than galantamine with IC values of 3.51 ± 0.80 µM and 2.90 ± 0.56 µM, respectively. The Lineweaver-Burk plots of compounds and indicated they were mixed-mode inhibitors. Compounds and have the potential to be employed as lead compounds for the development of new drugs or medicinal supplements to treat AD.