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Research
Julio Alonso-Padilla
Instituto de Salud Global Barcelona
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4466-7969
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 9 alkaloids derived from plants of the Amaryllidaceae family.
Methods: the activity of each alkaloid was assessed by means of an anti-T. cruzi phenotypic assay. We further evaluated the compounds that inhibited the parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity.
Results: we identified a single compound (hippeastrine 2) 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 (IC50 = 3.31 μM).
Conclusions: results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.
Keywords
Chagas disease; Trypanosoma cruzi; alkaloids; Amaryllidaceae; hippeastrine; phenotypic assays; cytotoxicity.
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CURRENT STATUS: Published
View the published article at Parasites & Vectors.
Version 4
Posted 16 May, 2020
No community comments so far
Editorial decision: Accept but needs final editing
On 30 May, 2020
Editor assigned
On 04 May, 2020
Submission checks complete
On 03 May, 2020
Editor invited
On 03 May, 2020
No comments provided
Editorial decision: Major Revision
On 27 Apr, 2020
Review #2 received
Received 24 Apr, 2020
Review #1 received
Received 20 Apr, 2020
Reviewer #2 agreed
On 19 Apr, 2020
Reviewer #1 agreed
On 17 Apr, 2020
Reviewers invited
Invitations sent on 14 Apr, 2020
Editor assigned
On 06 Apr, 2020
Submission checks complete
On 05 Apr, 2020
Editor invited
On 05 Apr, 2020
No comments provided
Editorial decision: Minor Revision
On 03 Apr, 2020
Review #1 received
Received 01 Apr, 2020
Review #2 received
Received 01 Apr, 2020
Reviewer #2 agreed
On 23 Mar, 2020
Reviewer #1 agreed
On 21 Mar, 2020
Reviewers invited
Invitations sent on 20 Mar, 2020
Editor assigned
On 19 Mar, 2020
Submission checks complete
On 18 Mar, 2020
Editor invited
On 18 Mar, 2020
No comments provided
Editorial decision: Major Revision
On 27 Feb, 2020
Review #3 received
Received 26 Feb, 2020
Review #2 received
Received 16 Feb, 2020
Reviewer #2 agreed
On 05 Feb, 2020
Reviewer #3 agreed
On 05 Feb, 2020
Review #1 received
Received 27 Jan, 2020
Reviewer #1 agreed
On 23 Jan, 2020
Reviewers invited
Invitations sent on 22 Jan, 2020
First submitted
On 18 Jan, 2020
Editor invited
On 18 Jan, 2020
Editor assigned
On 18 Jan, 2020
Submission checks complete
On 17 Jan, 2020
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Parasitology
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A new preprint design is coming!
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See the published version of this preprint at Parasites & Vectors.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Julio Alonso-Padilla
Instituto de Salud Global Barcelona
Corresponding Author
ORCiD: https://orcid.org/0000-0003-4466-7969
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Parasites & Vectors.
Version 4
Posted 16 May, 2020
No community comments so far
Editorial decision: Accept but needs final editing
On 30 May, 2020
Editor assigned
On 04 May, 2020
Submission checks complete
On 03 May, 2020
Editor invited
On 03 May, 2020
No comments provided
Editorial decision: Major Revision
On 27 Apr, 2020
Review #2 received
Received 24 Apr, 2020
Review #1 received
Received 20 Apr, 2020
Reviewer #2 agreed
On 19 Apr, 2020
Reviewer #1 agreed
On 17 Apr, 2020
Reviewers invited
Invitations sent on 14 Apr, 2020
Editor assigned
On 06 Apr, 2020
Submission checks complete
On 05 Apr, 2020
Editor invited
On 05 Apr, 2020
No comments provided
Editorial decision: Minor Revision
On 03 Apr, 2020
Review #1 received
Received 01 Apr, 2020
Review #2 received
Received 01 Apr, 2020
Reviewer #2 agreed
On 23 Mar, 2020
Reviewer #1 agreed
On 21 Mar, 2020
Reviewers invited
Invitations sent on 20 Mar, 2020
Editor assigned
On 19 Mar, 2020
Submission checks complete
On 18 Mar, 2020
Editor invited
On 18 Mar, 2020
No comments provided
Editorial decision: Major Revision
On 27 Feb, 2020
Review #3 received
Received 26 Feb, 2020
Review #2 received
Received 16 Feb, 2020
Reviewer #2 agreed
On 05 Feb, 2020
Reviewer #3 agreed
On 05 Feb, 2020
Review #1 received
Received 27 Jan, 2020
Reviewer #1 agreed
On 23 Jan, 2020
Reviewers invited
Invitations sent on 22 Jan, 2020
First submitted
On 18 Jan, 2020
Editor invited
On 18 Jan, 2020
Editor assigned
On 18 Jan, 2020
Submission checks complete
On 17 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Parasitology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Parasites & Vectors.
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 9 alkaloids derived from plants of the Amaryllidaceae family.
Methods: the activity of each alkaloid was assessed by means of an anti-T. cruzi phenotypic assay. We further evaluated the compounds that inhibited the parasite growth on two distinct cytotoxicity assays to discard those that were toxic to host cells and assure parasite selectivity.
Results: we identified a single compound (hippeastrine 2) 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 (IC50 = 3.31 μM).
Conclusions: results reported here suggest that natural products are an interesting source of new compounds for the development of drugs against Chagas disease.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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