Primaquine and Chloroquine Fumardiamides as Promising Antiplasmodial Agents

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Maja BeusBranka Zorc

Abstract

This paper describes a continuation of our efforts in the pursuit of novel antiplasmodial agents with optimized properties. Following our previous discovery of biologically potent asymmetric primaquine (PQ) and halogenaniline fumardiamides (1-6), we now report their significant in vitro activity against the hepatic stages of Plasmodium parasites. Furthermore, we successfully prepared chloroquine (CQ) analogue derivatives (11-16) and evaluated their activity against both the hepatic and erythrocytic stages of Plasmodium. Our results have shown that PQ fumardiamides (1-6) exert both higher activity against P.berghei hepatic stages and lower toxicity against human hepatoma cells than the parent drug and CQ derivatives (11-16). The favourable cytotoxicity profile of the most active compounds, 5 and 6, was corroborated by assays performed on human cells (human breast adenocarcinoma (MCF-7) and non-tumour embryonic kidney cells (HEK293T)), even when glucose-6-phosphate dehydrogenase (G6PD) was inhibited. The activity of CQ fumardiamides on P. falciparum erythrocytic stages was higher than that of PQ derivatives, comparable to CQ against CQ-resistant strain PfDd2, but lower than CQ when tested on the CQ-sensitive strain Pf3D7. In addi...Continue Reading

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Citations

Dec 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana Teresa SilvaPaula Gomes

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Methods Mentioned

BETA
column chromatography
Assay

Software Mentioned

Chemicalize
R
. org
package
GraphPad Prism
ZINC
SwissADME
drc

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