NDLI: In vitro antiplasmodial activity, pharmacokinetic profiles and interference in isoprenoid pathway of 2-aniline-3-hydroxy-1.4-naphthoquinone derivatives

Content Provider	Springer Nature : BioMed Central
Author	de Sena Pereira, Valeska S. da Silva Emery, Flávio Lobo, Lis Nogueira, Fátima Oliveira, Jonas I. N. Fulco, Umberto L. Albuquerque, Eudenilson L. Katzin, Alejandro M. de Andrade-Neto, Valter F.
Abstract	Background Plasmodium 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. Results The 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 44.5 μM. The cell viability in vitro against RAW Cell Line displayed IC50 = 483.5 and 714.9 μM, whereas, in primary culture tests using murine macrophages, IC50 were 315.8 and 532.6 μM 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 300 mg/kg. It is suggested that this drug seems to inhibit the biosynthesis of isoprenic compounds, particularly the menaquinone and tocopherol. Conclusions These 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.
Related Links	https://malariajournal.biomedcentral.com/counter/pdf/10.1186/s12936-018-2615-8.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
ISSN	14752875
DOI	10.1186/s12936-018-2615-8
Journal	Malaria Journal
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2018-12-19
Access Restriction	Open
Subject Keyword	Parasitology Tropical Medicine Infectious Diseases Entomology Microbiology Public Health Plasmodium falciparum Antimalarial drugs Hydroxy-naphthoquinones ADME predictions Isoprenoid pathway
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology
Journal Impact Factor	2.4/2023
5-Year Journal Impact Factor	2.6/2023

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