| Full text | |
| Author(s): |
de Sena Pereira, Valeska S.
[1, 2]
;
Emery, Flavio da Silva
[3]
;
Lobo, Lis
[4]
;
Nogueira, Fatima
[4]
;
Oliveira, Jonas I. N.
[5]
;
Fulco, Umberto L.
[5]
;
Albuquerque, Eudenilson L.
[5]
;
Katzin, Alejandro M.
[6]
;
de Andrade-Neto, Valter F.
[1, 2]
Total Authors: 9
|
| Affiliation: | [1] Univ Fed Rio Grande do Norte, Dept Microbiol & Parasitol, Lab Biol Malaria & Toxoplasmose LABMAT, Natal, RN - Brazil
[2] Univ Fed Rio Grande do Norte, Postgrad Program Biochem, Natal, RN - Brazil
[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, Ribeirao Preto, SP - Brazil
[4] Univ Nova Lisboa, IHMT, Unidade Ensino & Invest Parasitol Med, GHTM, Lisbon - Portugal
[5] Univ Fed Rio Grande do Norte, Dept Biofis & Farmacol, Natal, RN - Brazil
[6] Univ Sao Paulo, Ctr Ciencias Biomed, Dept Parasitol, Sao Paulo, SP - Brazil
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | Malaria Journal; v. 17, DEC 19 2018. |
| Web of Science Citations: | 0 |
| Abstract | |
BackgroundPlasmodium falciparum has shown multidrug resistance, leading to the necessity for the development of new drugs with novel targets, such as the synthesis of isoprenic precursors, which are excellent targets because the pathway is different in several steps when compared with the human host. Naphthoquinone derivatives have been described as potentially promising for the development of anti-malarial leader molecules. In view of that, the focus in this work is twofold: first, evaluate the in vitro naphthoquinone antiplasmodial activity and cytotoxicity; secondly, investigate one possible action mechanism of two derivatives of hydroxy-naphthoquinones.ResultsThe two hydroxy-naphthoquinones derivatives have been tested against P. falciparum in vitro, using strains of parasites chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2), causing 50% inhibition of parasite growth with concentrations that varied from 7 to 44.5M. The cell viability in vitro against RAW Cell Line displayed IC50=483.5 and 714.9M, whereas, in primary culture tests using murine macrophages, IC50 were 315.8 and 532.6M for the two selected compounds, causing no haemolysis at the doses tested. The in vivo acute toxicity assays exhibited a significant safety margin indicated by a lack of systemic and behavioural toxicity up to 300mg/kg. It is suggested that this drug seems to inhibit the biosynthesis of isoprenic compounds, particularly the menaquinone and tocopherol.ConclusionsThese derivatives have a high potential for the development of new anti-malarial drugs since they showed low toxicity associated to a satisfactory antiplasmodial activity and possible inhibition of a metabolic pathway distinct from the pathways found in the mammalian host. (AU) | |
| FAPESP's process: | 14/23417-7 - Biosynthesis of isoprenoids in Plasmodium falciparum: evaluation of possible targets for to obtain new anti-malarial drugs |
| Grantee: | Alejandro Miguel Katzin |
| Support Opportunities: | Regular Research Grants |