Jirapast Sichaem
Scientific Tracks Abstracts: J Neurol Neurophysiol
Alzheimer’s disease (AD) is the most common cause of neurodegenerative disorder and dementia in elderly people. The
cholinergic hypothesis proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine (ACh)
in the brain. In addition, a substrate non-specific butyrylcholinesterase (BChE) is also found to play a significant role in the
hydrolysis of ACh. Moreover, there are several reports that have revealed that the reduction of AChE activity can be compensated
for BChE activity. Thus, all of the above reasons have stimulated a great interest in screening natural cholinesterase (ChE)
inhibitors as lead compounds for the intended treatment of AD as they should have significant inhibition activities towards
both AChE and BChE.
Previous reports have shown that some furoquinoline alkaloids and other constituents of the plants from Rutaceae family
have ChEs activities revealed to the treatment of AD. Therefore, the successive extraction and isolation of bioactive ChE
inhibiting compounds from the plants of this family were interesting, as they can themselves be active and used directly
as a drug. Evodia lepta (Spreng.) Merr. (Rutaceae) is a traditional medicinal plant used for the treatment of arthritis, fever,
chickenpox, epidemic influenza, meningitis, infectious hepatitis, antipruritic, depurative and febrifuge diseases. Several
furoquinoline alkaloids, flavonoids and chromones have been also reported from this plant in previous studies.
Three new furoquinoline alkaloids (1-3) along with six known furoquinoline compounds (4-9) were isolated from the
leaves of Evodia lepta based on bioassay-guided fractionation and chromatographic techniques. All isolates were evaluated for
their in vitro cholinesterase (ChEs) inhibitory activities, in which compounds 7 and 5 exhibited the highest activity toward
AChE and BChE, respectively. Lineweaver-Burk plots indicated that 5 and 7 were mixed mode inhibitors of both ChE enzymes.
Finally, the molecular docking studies on the binding sites of AChE and BChE were performed in order to afford a molecular
insight into the mode of action of these active compounds in a good agreement with their anti-ChE results. Therefore, this
information can help in designing a new inhibitor in the class of furoquinoline alkaloids in against Alzheimer’s disease.
Jirapast Sichaem has completed his PhD at the age of 26 years from Chulalongkorn University. He is doing postdoctoral studies in the field of anticholinesterase
compounds from Thai medicinal plants at Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University. He has
published more than 22 papers in scientific journals.
