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Planta Med 2015; 81(06): 517-524
DOI: 10.1055/s-0034-1383261
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Alkaloids from Psychotria Target Sirtuins: In Silico and In Vitro Interaction Studies

Lionel Sacconnay   *
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland
,
Lucie Ryckewaert   *
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland
,
Carolina dos Santos Passos
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland
,
Maria Cristina Guerra
2   Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Lucilia Kato
3   Laboratório de Bioatividade Molecular, Instituto de Química, Universidade Federal de Goiás, UFG, Goiânia, GO, Brazil
,
Cecilia Maria Alves de Oliveira
3   Laboratório de Bioatividade Molecular, Instituto de Química, Universidade Federal de Goiás, UFG, Goiânia, GO, Brazil
,
Amélia Henriques
4   Laboratório Farmacognosia, Departamento de Produção de Matéria-Prima, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Pierre-Alain Carrupt
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland
,
Claudia Simões-Pires
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland
,
Alessandra Nurisso
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland
› Author Affiliations
Further Information

Publication History

received 08 July 2014
revised 23 September 2014

accepted 06 October 2014

Publication Date:
03 December 2014 (online)

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Abstract

Epigenetic enzymes such as histone deacetylases play a crucial role in the development of ageing-related diseases. Among the 18 histone deacetylase isoforms found in humans, class III histone deacetylases, also known as sirtuins, seem to be promising targets for treating neurodegenerative conditions. Recently, Psychotria alkaloids, mainly monoterpene indoles, have been reported for their inhibitory properties against central nervous system cholinesterase and monoamine oxidase proteins. Given the multifunctional profile of these alkaloids in the central nervous system, and the fact that the indole scaffold has been previously associated with sirtuin inhibition, we hypothesized that these indole derivatives could also interact with sirtuins. In the present study, alkaloids previously isolated from Psychotria spp. were evaluated for their potential interaction with human sirtuin 1 and sirtuin 2 by molecular docking and molecular dynamics simulation approaches. The in silico results allowed for the selection of five potentially active compounds, namely, prunifoleine, 14-oxoprunifoleine, E-vallesiachotamine, Z-vallesiachotamine, and vallesiachotamine lactone. The sirtuin inhibition of these compounds was confirmed in vitro in a dose-response manner, with preliminary information on their pharmacokinetics properties.

Key words

alkaloids - Psychotria spp. - Rubiaceae - sirtuins - inhibitors - docking - molecular dynamics

* These authors contributed equally to the work.


Supporting Information

 

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