In Vitro and In Silico Evaluation of Cholinesterase Inhibition by Alkaloids Obtained from Branches of Abuta panurensis Eichler

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 10; p. 3138
• Main Authors: da Silva Mesquita, Rochelly, Kyrylchuk, Andrii, Cherednichenko, Anton, Costa Sá, Ingrity Suelen, Macedo Bastos, Lílian, Moura Araújo da Silva, Felipe, Saraiva Nunomura, Rita de Cássia, Grafov, Andriy
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.05.2022; MDPI
• Subjects: Abuta panurensis; Acetylcholinesterase; Acetylcholinesterase - metabolism; Alkaloids; Alkaloids - chemistry; Alkaloids - pharmacology; Alzheimer's disease; butyrylcholinesterase; Butyrylcholinesterase - chemistry; Cholinesterase; Cholinesterase inhibitors; Endemic species; Enzymes; High-performance liquid chromatography; inhibitory activity; Liquid chromatography; Magnetic resonance spectroscopy; Menispermaceae; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Natural products; NMR; NMR spectroscopy; Nuclear magnetic resonance; Rainforests; acetylcholinesterase; butyrylcholinesterase; molecular docking; inhibitory activity; Abuta panurensis; alkaloids
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27103138

Alkaloids are natural products known as ethnobotanicals that have attracted increasing attention due to a wide range of their pharmacological properties. In this study, cholinesterase inhibitors were obtained from branches of Eichler (Menispermaceae), an endemic species from the Amazonian rainforest. Five alkaloids were isolated, and their structure was elucidated by a combination of 1D and 2D H and C NMR spectroscopy, HPLC-MS, and high-resolution MS: Lindoldhamine isomer / 569.2674 ( ), stepharine / 298.1461 ( ), palmatine / 352.1616 ( ), 5- -methylmaytenine / 420.2669 ( ) and the - -feruloyltyramine / 314.1404 ( ). The compounds , , and were isolated from for the first time. Interaction of the above-mentioned alkaloids with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes was investigated in silico by molecular docking and molecular dynamics. The molecules under investigation were able to bind effectively with the active sites of the AChE and BChE enzymes. The compounds - demonstrated in vitro an inhibitory effect on acetylcholinesterase with IC values in the range of 19.55 µM to 61.24 µM. The data obtained in silico corroborate the results of AChE enzyme inhibition.