Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity.
Alkaloids
Amaryllidaceae
Chagas disease
Cytotoxicity
Hippeastrine
Phenotypic assays
Trypanosoma cruzi
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
10 Jun 2020
10 Jun 2020
Historique:
received:
18
01
2020
accepted:
04
06
2020
entrez:
12
6
2020
pubmed:
12
6
2020
medline:
11
2
2021
Statut:
epublish
Résumé
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects ~7 million people worldwide. Development of new drugs to treat the infection remains a priority since those currently available have frequent side effects and limited efficacy at the chronic stage. Natural products provide a pool of diversity structures to lead the chemical synthesis of novel molecules for this purpose. Herein we analyzed the anti-T. cruzi activity of nine alkaloids derived from plants of the family Amaryllidaceae. The activity of each alkaloid was assessed by means of an anti-T. cruzi phenotypic assay. We further evaluated the compounds that inhibited parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity. We identified a single compound (hippeastrine) that was selectively active against the parasite yielding selectivity indexes of 12.7 and 35.2 against Vero and HepG2 cells, respectively. Moreover, it showed specific activity against the amastigote stage (IC Results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.
Sections du résumé
BACKGROUND
BACKGROUND
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a neglected disease that affects ~7 million people worldwide. Development of new drugs to treat the infection remains a priority since those currently available have frequent side effects and limited efficacy at the chronic stage. Natural products provide a pool of diversity structures to lead the chemical synthesis of novel molecules for this purpose. Herein we analyzed the anti-T. cruzi activity of nine alkaloids derived from plants of the family Amaryllidaceae.
METHODS
METHODS
The activity of each alkaloid was assessed by means of an anti-T. cruzi phenotypic assay. We further evaluated the compounds that inhibited parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity.
RESULTS
RESULTS
We identified a single compound (hippeastrine) that was selectively active against the parasite yielding selectivity indexes of 12.7 and 35.2 against Vero and HepG2 cells, respectively. Moreover, it showed specific activity against the amastigote stage (IC
CONCLUSIONS
CONCLUSIONS
Results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.
Identifiants
pubmed: 32522289
doi: 10.1186/s13071-020-04171-6
pii: 10.1186/s13071-020-04171-6
pmc: PMC7288428
doi:
Substances chimiques
Amaryllidaceae Alkaloids
0
Phytochemicals
0
Trypanocidal Agents
0
hippeastrine
477-17-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
299Subventions
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2017SGR00924
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2017SGR604
Organisme : Instituto de Salud Carlos III
ID : RICET RD12/0018/0010
Organisme : CYTED Ciencia y Tecnología para el Desarrollo
ID : 416RT0511
Organisme : Departament de Salut, Generalitat de Catalunya
ID : PERIS 2016-2010 SLT008/18/00132
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : "Centro de Excelencia Severo Ochoa 2019-2023" CEX2018-000806-S
Références
Bioorg Med Chem. 2016 Nov 1;24(21):5418-5422
pubmed: 27624525
Expert Opin Investig Drugs. 2000 Oct;9(10):2393-402
pubmed: 11060814
Lancet Infect Dis. 2001 Sep;1(2):92-100
pubmed: 11871482
J Nat Prod. 2012 Sep 28;75(9):1643-7
pubmed: 22917000
Drug Saf. 2018 Nov;41(11):1035-1048
pubmed: 30006773
Expert Rev Mol Diagn. 2017 Jul;17(7):699-710
pubmed: 28582629
N Engl J Med. 2014 May 15;370(20):1899-908
pubmed: 24827034
Arch Pharm Res. 2015;38(5):691-704
pubmed: 25336106
Nature. 2016 Sep 8;537(7619):229-233
pubmed: 27501246
Planta Med. 1998 Oct;64(7):679-80
pubmed: 9810280
PLoS Negl Trop Dis. 2009;3(2):e384
pubmed: 19238193
Phytochemistry. 2004 Jul;65(14):2113-8
pubmed: 15279981
J Biomol Screen. 1999;4(2):67-73
pubmed: 10838414
Molecules. 2017 Oct 12;22(10):
pubmed: 29023425
Cell Stem Cell. 2017 Aug 3;21(2):274-283.e5
pubmed: 28736217
Chirality. 2017 Sep;29(9):486-499
pubmed: 28649696
Sci Rep. 2015 Mar 05;5:8771
pubmed: 25740547
Eur J Med Chem. 2013 May;63:722-30
pubmed: 23567962
Mol Cell Biol. 1986 Jun;6(6):2279-83
pubmed: 3785197
PLoS Negl Trop Dis. 2015 Jan 23;9(1):e0003493
pubmed: 25615687
Mol Med Rep. 2017 Feb;15(2):941-947
pubmed: 28035421
PLoS Negl Trop Dis. 2015 Sep 22;9(9):e0004014
pubmed: 26394211
Nat Prod Commun. 2012 Dec;7(12):1677-88
pubmed: 23413581
Nat Rev Microbiol. 2019 Oct;17(10):607-620
pubmed: 31444481
J Pharm Biomed Anal. 2012 Nov;70:13-25
pubmed: 22673940
Antimicrob Agents Chemother. 1996 Nov;40(11):2592-7
pubmed: 8913471
Alkaloids Chem Biol. 2006;63:87-179
pubmed: 17133715
Clin Infect Dis. 2016 Oct 15;63(8):1056-1062
pubmed: 27432838
Antimicrob Agents Chemother. 2010 Nov;54(11):4896-9
pubmed: 20823286
Bioorg Med Chem Lett. 2017 Nov 15;27(22):4943-4951
pubmed: 29033234
Alkaloids Chem Biol. 2020;83:113-185
pubmed: 32098649
Phytochemistry. 2004 Dec;65(23):3143-9
pubmed: 15541744
Molecules. 2011 Aug 18;16(8):7097-104
pubmed: 21852767
Planta Med. 2001 Mar;67(2):191-3
pubmed: 11301878
J Am Coll Cardiol. 2017 Feb 28;69(8):939-947
pubmed: 28231946
Molecules. 2017 Dec 09;22(12):
pubmed: 29232852
Trop Med Infect Dis. 2019 May 17;4(2):
pubmed: 31108888
Planta Med. 1995 Feb;61(1):77-9
pubmed: 7701000
J Immunol Methods. 1993 Mar 15;160(1):81-8
pubmed: 7680699
Nat Prod Rep. 2011 Apr;28(4):809-23
pubmed: 21290079
Influenza Other Respir Viruses. 2013 Nov;7(6):922-31
pubmed: 23136954
Nat Prod Commun. 2014 Aug;9(8):1193-210
pubmed: 25233606
Molecules. 2017 Aug 31;22(9):
pubmed: 28858260