Alsinol, an arylamino alcohol derivative active against Plasmodium , Babesia , Trypanosoma , and Leishmania : past and n
- PDF / 694,253 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 3 Downloads / 168 Views
TREATMENT AND PROPHYLAXIS - ORIGINAL PAPER
Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes Maria H Arias 1 & Miguel Quiliano 2 & Sandra Bourgeade-Delmas 3 & Isabelle Fabing 4 & Isabelle Chantal 5,6 & David Berthier 5,6 & Cécile Minet 5,6 & Veronique Eparvier 7 & Jonathan Sorres 7 & Didier Stien 8 & Silvia Galiano 9 & Ignacio Aldana 9 & Alexis Valentin 3 & Giovanny Garavito 1 & Eric Deharo 3,10 Received: 21 November 2019 / Accepted: 26 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Antiprotozoan . Alsinol . Babesia . Leishmania . Plasmodium falciparum gametocytes . Trypanosoma
Section Editor: Ramaswamy Kalyanasundaram * Giovanny Garavito [email protected] 1
2
5
UMR INTERTRYP, CIRAD, F-34398 Montpellier, France
6
INTERTRYP, Univ Montpellier, CIRAD, IRD, Montpellier, France
7
Facultad de Ciencias, Departamento de Farmacia, Grupo de Investigación FaMeTra (Farmacología de la Medicina Tradicional y Popular), Universidad Nacional de Colombia, Sede Bogotá, Carrera 30 45-03, Bogotá D.C. 111321, Colombia
ICSN-CNRS UPR 2301 Équipe “Métabolites de végétaux et micro-organismes associés: isolement, synthèse et bioactivité”, 91198 cedex Gif-sur-Yvette, France
8
Faculty of Health Sciences, Centre for Research and Innovation, Universidad Peruana de Ciencias Aplicadas (UPC), 15023 Lima, Peru
Laboratoire de Biodiversité et Biotechnologie Microbienne, LBBM, Observatoire Océanologique, CNRS, Sorbonne Université, 66650 Banyuls-sur-mer, France
9
Facultad de Farmacia y Nutrición, Departamento de Química Orgánica y Farmacéutica, Universidad de Navarra, C
Data Loading...
