Isoquinoline alkaloids from the roots of Zanthoxylum rigidum as multi-target inhibitors of cholinesterase, monoamine oxidase A and Aβ1-42 aggregation.

Bioorganic Chemistry
Erika PlazasLuis Enrique Cuca

Abstract

Multifactorial neurodegenerative disorders such as Alzheimer's disease (AD) are considered a growing public health problem due the rising incidence and low effectiveness of current treatments [6]. Since pharmacotherapy based on a single target has been insufficient for drug development in complex diseases, the emerging multi-target approach is a promising strategy for the search of new anti-AD drug candidates. Herein described natural isoquinoline alkaloids were investigated for multi-target activity on key mechanisms associated with the AD's pathogenesis, i.e. cholinergic depletion, beta amyloid (Aβ) aggregation and oxidative stress. Alkaloid isolation from root extract of Zanthoxylum rigidum was carried out using multi-step chromatography and TLC-bioautography against acetylcholinesterase (AChE) giving eight purified isoquinoline alkaloids. Isolated compounds were tested for inhibitory activity against cholinesterase (AChE and BChE), monoamine oxidase (MAO-A and B) and Aβ aggregation. Our study revealed two benzophenanthridine alkaloids, nitidine (5) and avicine (7), as the most potent multi-target candidates. Both showed dual cholinesterase inhibition, being more active against AChE over BChE, with IC50 values in sub-micromo...Continue Reading

References

Mar 15, 2003·International Psychogeriatrics·Nigel H GreigKumar Sambamurti
Dec 20, 2003·Organic & Biomolecular Chemistry·Keith JonesPhilip Whitfield
Aug 9, 2005·The International Journal of Neuropsychopharmacology·Roger M LaneAlbert Enz
Jan 13, 2006·British Journal of Pharmacology·W C Bowman
Jun 19, 2007·Archives of Biochemistry and Biophysics·Dale E EdmondsonAndrea Mattevi
Feb 9, 2010·Chemico-biological Interactions·Hay DvirJoel L Sussman
Dec 15, 2010·Behavioural Brain Research·Reinhard Schliebs, Thomas Arendt
Jan 1, 2000·Pharmaceutical Biology·O A Binutu, G A Cordell
Feb 7, 2013·Plant & Cell Physiology·Jillian M Hagel, Peter J Facchini
Nov 13, 2013·Molecular Diversity·Simone CarradoriAdriana Bolasco
Nov 19, 2013·The Journal of Pharmacy and Pharmacology·Eduardo Luis KonrathAmélia T Henriques
Apr 4, 2015·Acta Crystallographica. Section C, Structural Chemistry·Subramanya PingaliFlorastina Payton-Stewart
Sep 24, 2015·Pharmacological Reports : PR·Touqeer AhmedSeyed Mohammad Nabavi
Jun 8, 2017·Annals of Neurosciences·Alfredo Sanabria-CastroCecilia Monge-Bonilla
Jul 18, 2017·Acta Pharmacologica Sinica·Guo-Fang ChenH Eric Xu
Jul 18, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rona R Ramsay, Keith F Tipton
Dec 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Terrone L RosenberryFlorian Nachon
Jan 18, 2018·Clinical and Translational Medicine·Rona R RamsayMaria Laura Bolognesi
Feb 27, 2018·European Journal of Medicinal Chemistry·Anna AffiniHolger Stark
Jun 22, 2018·Bioorganic & Medicinal Chemistry Letters·Seung Cheol BaekHoon Kim
Aug 9, 2018·Frontiers in Pharmacology·Ming ChuYuedan Wang
Dec 7, 2018·ACS Chemical Neuroscience·Huan Wang, Haiyan Zhang
Feb 13, 2019·Bioorganic & Medicinal Chemistry·Pankaj MishraGautam Panda
Mar 10, 2019·European Journal of Medicinal Chemistry·Katarina ChalupovaKamil Kuca
May 20, 2019·European Journal of Medicinal Chemistry·Pengfei ZhangJinyi Xu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.