Indole Alkaloids and Semisynthetic Indole Derivatives as Multifunctional Scaffolds Aiming the Inhibition of Enzymes Related to Neurodegenerative Diseases – A Focus on Psychotria L. Genus

ISSN: 1873-5294 (Online)
ISSN: 1568-0266 (Print)

Volume 16, 30 Issues, 2016

Download PDF Flyer

Current Topics in Medicinal Chemistry

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 12th of 59 in Chemistry, Medicinal

Allen B. Reitz
Fox Chase Chemical Diversity Center, Inc.
Doylestown, PA

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 3.402
5 - Year: 3.632

Indole Alkaloids and Semisynthetic Indole Derivatives as Multifunctional Scaffolds Aiming the Inhibition of Enzymes Related to Neurodegenerative Diseases – A Focus on Psychotria L. Genus

Current Topics in Medicinal Chemistry, 14(8): 1056-1075.

Author(s): Luiz Carlos Klein-Junior, Carolina dos Santos Passos, Aline Pereira Moraes, Vinicius Galvao Wakui, Eduardo Luis Konrath, Alessandra Nurisso, Pierre-Alain Carrupt, Cecilia Maria Alves de Oliveira, Lucilia Kato and Amelia Teresinha Henriques.

Affiliation: Programa de Pos Graduacao em Ciencias Farmaceuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre – RS, Brazil.


Indole alkaloids and synthetic indole derivatives are well known for their therapeutic importance. In fact, preclinical and clinical studies had already demonstrated several pharmacological activities for these compounds. Here, we overview the multifunctional potential of these molecules for the inhibition of enzymes related to neurodegenerative disease: acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidases A and B (MAO-A and MAO-B). A focus will be given on Psychotria L. genus, considering its reported central effects. Finally, three Psychotria alkaloids, namely desoxycordiofoline (61), bahienoside A (64) and bufotenine (65), along with the synthetic indole derivatives (5S)- 5-(1H-indol-3-ylmethyl)imidazolidine-2,4-dione (66), 5-(1H-indol-3-ylmethyl)-2-thioxoimidazolin-4-one (67), 5-(1Hindol- 3-ylmethyl)-3-methyl-2-thioxoimidazolidin-4-one (68), and methyl 2-(aminoN-(2-(4-methylcyclohex-3-enyl)propan- 2-yl)methanethioamino)-3-(1H-indol-3-yl)propanoate (69), were evaluated in vitro regarding their interactions with AChE, BChE, MAO-A and MAO-B. It was observed that 66 and 68 were able to inhibit MAO-A activity with IC50 value of 8.23 and 0.07 μM. Molecular docking calculations were performed in order to understand the interactions between both ligands (66 and 68) and MAO-A. It was observed that the indole scaffold of both compounds bind into the MAO-A active site in the same orientation, establishing van der Waals contacts with lipophilic amino acids. Additionally, the hydantoin ring of 66 is able to interact by hydrogen bonds with two conserved water molecules in the MAO-A active site, while the methyl-thiohydantoin ring of 68 is within hydrogen bond distance from the hydrogen atom attached to the (N-5) of FAD cofactor. Taking together, our findings demonstrate that the indolyl-hydantoin and indolylmethyl-thiohydantoin rings might consists of good scaffolds for the development of new MAO-A inhibitors possessing neuroprotective properties.


Cholinesterases inhibition, indole alkaloids, indole derivatives, molecular docking, monoamine oxidases inhibition, multi-target scaffolds, neurodegenerative diseases, Psychotria.

Purchase Online Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 14
Issue Number: 8
First Page: 1056
Last Page: 1075
Page Count: 20
DOI: 10.2174/1568026614666140324142409
Global Biotechnology Congress 2016Drug Discovery and Therapy World Congress 2016

Related Journals

Webmaster Contact: Copyright © 2016 Bentham Science