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

被引：3

作者：

Bellei, Jessica Correa Bezerra ^{[1
]}

Glanzmann, Nicolas ^{[2
]}

Carpinter, Barbara Albuquerque ^{[1
]}

Renhe, Daniela Chaves ^{[1
]}

Marques, Carolina Brandi ^{[1
]}

Azevedo, Marina Rocha ^{[1
]}

Barreto, Livia Maria ^{[1
]}

Rocha, Vinicius Novaes ^{[3
]}

Nunes, Isabelle Karine da Costa ^{[4
]}

Pereira, Henrique Marcelo Gualberto ^{[4
]}

Coimbra, Elaine Soares ^{[1
]}

Coelho, Eduardo Antonio Ferraz ^{[5
]}

da Silva, Adilson David ^{[2
]}

Varotti, Fernando de Pilla ^{[6
]}

Scopel, Kezia Katiani Gorza ^{[1
]}

机构：

[1] Univ Fed Juiz de Fora, Res Ctr Parasitol, Dept Parasitol Microbiol & Immunol, BR-36036900 Juiz De Fora, MG, Brazil

[2] Univ Fed Juiz de Fora, Inst Exact Sci, Dept Chem, BR-36036900 Juiz De Fora, MG, Brazil

[3] Univ Fed Juiz de Fora, Res Ctr Pathol & Vet Histol, Dept Vet Med, BR-36036900 Juiz De Fora, MG, Brazil

[4] Univ Fed Rio de Janeiro, Technol Dev Support Lab, Chem Hub, BR-21941598 Rio De Janeiro, Brazil

[5] Univ Fed Minas Gerais, Fac Med, Postgrad Program Hlth Sci Infectol & Trop Med, Av Alfredo Balena 190, BR-30130100 Belo Horizonte, MG, Brazil

[6] Univ Fed Sao Joao del Rei, Res Ctr Biol Chem NQBio, Divinopolis, MG, Brazil

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2022年 / 355卷

关键词：

Malaria; Cerebral malaria; Quinoline derivative; Plasmodium falciparum; RAPID COLORIMETRIC ASSAY; ARTEMISININ RESISTANCE; FALCIPARUM-MALARIA; SILICO PREDICTION; DRUG DISCOVERY; TOXICITY; BERGHEI; SEQUESTRATION; PERMEABILITY; PATHOGENESIS;

D O I：

10.1016/j.cbi.2022.109848

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：10