Title
Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes
Date Issued
01 October 2020
Access level
open access
Resource Type
journal article
Author(s)
Arias M.H.
Bourgeade-Delmas S.
Fabing I.
Chantal I.
Berthier D.
Minet C.
Eparvier V.
Sorres J.
Stien D.
Galiano S.
Aldana I.
Valentin A.
Garavito G.
Deharo E.
Publisher(s)
Springer Science and Business Media Deutschland GmbH
Abstract
Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.
Start page
3503
End page
3515
Volume
119
Issue
10
Language
English
OCDE Knowledge area
Parasitología
Subjects
Scopus EID
2-s2.0-85089259748
PubMed ID
Source
Parasitology Research
ISSN of the container
09320113
Sponsor(s)
Alsinol is a drug designed in collaboration between UMR152 IRD-UPS and the Universidad de Navarra. It was supported by the Direction de la Valorisation au Sud (DVS) as part of the IRD Maturation projects program. They also acknowledge the support of Laboratoire d’Excellence (Labex) Parafrap N8ANR-11-LABX-0024 and the Chemical Institute of Toulouse (ICT, FR2599 CNRS), Integrated Screening Platform of Toulouse (PICT, IBISA).
This study was funded by the Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias) and the French Ministère des Affaires étrangères et du Développement international (MAEE) through ECOSNORD 2013 program [HERMES- 28693] and the Vicedecanatura de Investigación, Facultad de Ciencias, Universidad Nacional de Colombia. This work was supported by PIUNA Project-University of Navarra and Foundation CAN (grant number: 70391). The authors are grateful to the Institute of Tropical Health (ISTUN) of University of Navarra for the financial support and help. Acknowledgments
MH Arias is grateful to the Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias) for her doctoral scholarship (Convocatoria 647, Doctorados Nacionales 2014), M Quiliano is grateful to the “Programa Nacional de Innovación para la competitividad y productividad” (Innóvate-Perú) for his doctoral scholarship (grant 065-FINCYT-BDE-2014).
We wish to thank Elizabeth Elliott for editing the document and for illuminating conversations. Alsinol is a drug designed in collaboration between UMR152 IRD-UPS and the Universidad de Navarra. It was supported by the Direction de la Valorisation au Sud (DVS) as part of the IRD Maturation projects program. They also acknowledge the support of Laboratoire d?Excellence (Labex) Parafrap N8ANR-11-LABX-0024 and the Chemical Institute of Toulouse (ICT, FR2599 CNRS), Integrated Screening Platform of Toulouse (PICT, IBISA). MH Arias is grateful to the Departamento Administrativo de Ciencia, Tecnolog?a e Innovaci?n (Colciencias) for her doctoral scholarship (Convocatoria 647, Doctorados Nacionales 2014), M Quiliano is grateful to the ?Programa Nacional de Innovaci?n para la competitividad y productividad? (Inn?vate-Per?) for his doctoral scholarship (grant 065-FINCYT-BDE-2014).
Sources of information:
Directorio de Producción Científica
Scopus