A simple quinoline salt derivative is active in vitro against Plasmodiumfalciparum asexual blood stages and inhibits the development of cerebral malaria in murine model.

Autor: Bezerra Bellei JC; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Glanzmann N; Department of Chemistry, Institute of Exact Sciences, Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Carpinter BA; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Renhe DC; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Marques CB; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Azevedo MR; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Barreto LM; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Rocha VN; Research Center of Pathology and Veterinary Histology. Departament of Veterinary Medicine /Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Karine da Costa Nunes I; Technological Development Support Laboratory, Chemistry Hub, Federal University of Rio de Janeiro, Rio de Janeiro/RJ 21.941-598, Brazil., Gualberto Pereira HM; Technological Development Support Laboratory, Chemistry Hub, Federal University of Rio de Janeiro, Rio de Janeiro/RJ 21.941-598, Brazil., Coimbra ES; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., Ferraz Coelho EA; Postgraduation Program in Health Sciences, Infectology and Tropical Medicine, Faculty of Medicine, Federal University of Minas Gerais, Av. Alfredo Balena, 190, 30130-100, Belo Horizonte, Minas Gerais, Brazil., David da Silva A; Department of Chemistry, Institute of Exact Sciences, Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil., de Pilla Varotti F; Research Center on Biological Chemistry (NQBio)/Federal University of São João Del Rei, Divinópolis, MG, Brazil. Electronic address: varotti@ufsj.edu.br., Gorza Scopel KK; Research Center Parasitology. Departament of Parasitology, Microbiology and Immunology. Federal University of Juiz de Fora, Juiz de Fora/MG 36.036-900, Brazil. Electronic address: keziagscopel@gmail.com.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2022 Mar 01; Vol. 355, pp. 109848. Date of Electronic Publication: 2022 Feb 09.
DOI: 10.1016/j.cbi.2022.109848
Abstrakt: Chloroquine (CQ) was the most effective and widely used drug for the prophylaxis and treatment of severe and non-severe malaria. Although its prophylactic use has led to resistance to P. falciparum in all endemic countries, CQ still remains the drug of choice for the treatment of vivax malaria. Otherwise, the speed in which parasite resistance to available antimalarials rises and spreads in endemic regions points to the urgent need for the development of new antimalarials. Quinoline derivatives have been used as a tool in the search for new drugs and were investigated in the present study in an attempt to produce a HIT compound to avoid the cerebral malarial (CM). Seven compounds were synthesized, including three quinoline derivate salts. The cytotoxicity and antiplasmodial activity were assayed in vitro, highlighting compound 3 as a HIT, which also showed interaction with ferriprotoporphyrin IX similarly to CQ. Physicochemical and pharmacokinetic properties of absorption were found to be favorable when analyzed in silico. The in vivo assays, using the experimental cerebral malaria (ECM) model, showed important values of parasite growth inhibition on the 7th day-post infection (Q15 15 mg/kg: 76.9%, Q30 30 mg/kg: 90,1% and Q50 50 mg/kg: 92,9%). Compound 3 also showed significant protection against the development of CM, besides hepatic and renal parameters better than CQ. In conclusion, this quinoline derivative demonstrated promising activity for the treatment of malaria and was able to avoid the development of severe malaria in mice.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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