Biological evaluation of hydroxynaphthoquinones as anti-malarials

Autor(es)

Schuck, Desiree C. ^[1] ; Ferreira, Sabrina B. ^{[2, 3]} ; Cruz, Laura N. ^[1] ; da Rocha, David R. ^[2] ; Moraes, Miriam S. ^[1] ; Nakabashi, Myna ^[1] ; Rosenthal, Philip J. ^[4] ; Ferreira, Vitor F. ^[2] ; Garcia, Celia R. S. ^{[5, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Fisiol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Fluminense, Dept Quim Organ, BR-24020141 Niteroi, RJ - Brazil

^[3] Univ Fed Rio de Janeiro, Dept Quim Organ, BR-27930560 Macae - Brazil

^[4] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 - USA

^[5] Univ Sao Paulo, Inst Biociencias, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Malaria Journal; v. 12, JUL 10 2013.
• Citações Web of Science: 25

Resumo

Background: The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone (R), an important drug for the treatment and prevention of malaria. Methods: Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation. Potential cytotoxicity in HEK293T cells was assessed using the MTT assay. Changes in mitochondrial membrane potential of Plasmodium were measured using the fluorescent dye Mitrotracker Red CMXROS. Results: Four compounds demonstrated IC(50)s in the mid-micromolar range, and the most active compound, N3, had an IC50 of 443 nM. N3 disrupted mitochondrial membrane potential, and after 1 hour presented an IC50 Delta Psi mit of 16 mu M. In an in vitro cytotoxicity assay using HEK 293T cells N3 demonstrated no cytotoxicity at concentrations up to 16 mu M. Conclusions: N3 was a potent inhibitor of mitochondrial electron transport, had nanomolar activity against cultured Plasmodium falciparum and showed minimal cytotoxicity. N3 may serve as a starting point for the design of new hydroxynaphthoquinone anti-malarials. (AU)

• Processo FAPESP: 07/52924-0 - Genômica funcional em Plasmodium
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático