Lobeline: A multifunctional alkaloid modulates cholinergic and glutamatergic activities.

Autor: Remya C; Department of Biotechnology and Microbiology, Kannur University, Thalassery, Kerala, India.; Laboratory for Computational and Structural Biology, Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India., Dileep KV; Laboratory for Computational and Structural Biology, Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India., Variyar EJ; Department of Biotechnology and Microbiology, Kannur University, Thalassery, Kerala, India.; Inter University Centre for Bioscience, Kannur University, Thalassery, Kerala, India., Omkumar RV; Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India., Sadasivan C; Department of Biotechnology and Microbiology, Kannur University, Thalassery, Kerala, India.; Inter University Centre for Bioscience, Kannur University, Thalassery, Kerala, India.
Jazyk: angličtina
Zdroj: IUBMB life [IUBMB Life] 2023 Oct; Vol. 75 (10), pp. 844-855. Date of Electronic Publication: 2023 Jun 19.
DOI: 10.1002/iub.2762
Abstrakt: Developing drugs for Alzheimer's disease (AD) is an extremely challenging task due to its devastating pathology. Previous studies have indicated that natural compounds play a crucial role as lead molecules in the development of drugs. Even though, there are remarkable technological advancements in the isolation and synthesis of natural compounds, the targets for many of them are still unknown. In the present study, lobeline, a piperidine alkaloid has been identified as a cholinesterase inhibitor through chemical similarity assisted target fishing method. The structural similarities between lobeline and donepezil, a known acetylcholinesterase (AChE) inhibitor encouraged us to hypothesize that lobeline may also exhibit AChE inhibitory properties. It was further confirmed by in silico, in vitro and biophysical studies that lobeline could inhibit cholinesterase. The binding profiles indicated that lobeline has a higher affinity for AChE than BChE. Since excitotoxicity is one of the major pathological events associated with AD progression, we also investigated the neuroprotective potential of lobeline against glutamate mediated excitotoxicity in rat primary cortical neurons. The cell based NMDA receptor (NMDAR) assay with lobeline suggested that neuroprotective potential of lobeline is mediated through the blockade of NMDAR activity.
(© 2023 International Union of Biochemistry and Molecular Biology.)
Databáze: MEDLINE
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