Design, Synthesis and Biological Evaluation of Indole Derivatives as Cholinesterase Inhibitors for the Treatment of Alzhermer’s Disease
Abstract
In this research, three groups of indole derivatives such as N-(N-piperidylethyl)indoles, N-(N-pyrrolidyl-ethyl)indoles and N-(chlroakyl)indoles were designed and efficiently synthesized by a simple method under mild reaction conditions to afford twenty-two compounds in moderate to excellent yields. Furthermore, all synthesized compounds were evaluated for their acetylcholinesterase inhibitory activity that contributes to Alzheimer's disease. The results found that 5-bromo-1-(3-chloropropyl)-1H-indole (JJIN-3d) showed promising acetylcholinesterase inhibitory activity with %inhibition value of 73.53 ± 0.30. Thus, the compound JJIN-3d could potentially be a lead compound for the development of a novel drug for the treatment Alzheimer’s disease. Keywords : indole derivatives ; acetylcholinesterase inhibitory activity ; Alzheimer’s diseaseReferences
Alzheimer’s Disease International. (2019). World Alzheimer Report 2019: Attitudes to dementia. Retrieved January 29, 2020, from https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf
Burns, A., & Iliffe, S. (2009). Alzheimer’s disease. British Medical Journal, 338, 467-471.
Institute of Neurology, Department of Medical Services, Ministry of Public Health. (2019). Retrieved January 29, 2020, from https://pr.moph.go.th/?url=pr/detail/2/02/132212
Khorana, N., Changwichit, K., Ingkaninan, K., & Utsintong, M. (2012). Prospective acetylcholinesterase
inhibitory activity of indole and its analogs. Bioorganic and Medicianl Chemistry Letters, 22, 2885-2888.
Lomlim, L., & Nounnai, T. (2011). A new approach to the development of acetylcholine esterine inhibitors for Alzheimer's disease. Thai Pharmaceutical and Health Science Journal, 6, 157-173. (in Thai)
Queiroz, M.M.F., Queiroz, E.F., Zeraik, M.L., Ebrahimi, S.N., Marcourt, L., Cuendet, M., Castro-Gamboa, I.,
Hamburger, M., Bolzani, V. da. S., & Wolfender, J.-L. (2014). Chemical composition of
the bark of Tetrapterys mucronata and identification of acetylcholinesterase inhibitory constituents.
Journal of Natural Product, 77, 650-656.
Sukying, C. (2012). Dementia. In M. Lortrakul, & P. Sukhanit. (Eds.), Psychiatry. (pp. 80-94). Bangkok: Sawichankan Printing. (in Thai)
Burns, A., & Iliffe, S. (2009). Alzheimer’s disease. British Medical Journal, 338, 467-471.
Institute of Neurology, Department of Medical Services, Ministry of Public Health. (2019). Retrieved January 29, 2020, from https://pr.moph.go.th/?url=pr/detail/2/02/132212
Khorana, N., Changwichit, K., Ingkaninan, K., & Utsintong, M. (2012). Prospective acetylcholinesterase
inhibitory activity of indole and its analogs. Bioorganic and Medicianl Chemistry Letters, 22, 2885-2888.
Lomlim, L., & Nounnai, T. (2011). A new approach to the development of acetylcholine esterine inhibitors for Alzheimer's disease. Thai Pharmaceutical and Health Science Journal, 6, 157-173. (in Thai)
Queiroz, M.M.F., Queiroz, E.F., Zeraik, M.L., Ebrahimi, S.N., Marcourt, L., Cuendet, M., Castro-Gamboa, I.,
Hamburger, M., Bolzani, V. da. S., & Wolfender, J.-L. (2014). Chemical composition of
the bark of Tetrapterys mucronata and identification of acetylcholinesterase inhibitory constituents.
Journal of Natural Product, 77, 650-656.
Sukying, C. (2012). Dementia. In M. Lortrakul, & P. Sukhanit. (Eds.), Psychiatry. (pp. 80-94). Bangkok: Sawichankan Printing. (in Thai)
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Published
2020-09-01
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