Disclosure of cinnamic acid/4,9-diaminoacridine conjugates as multi-stage antiplasmodial hits.
Bioorg Med Chem
; 104: 117714, 2024 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-38582046
ABSTRACT
4,9-diaminoacridines with reported antiplasmodial activity were coupled to different trans-cinnamic acids, delivering a new series of conjugates inspired by the covalent bitherapy concept. The new compounds were more potent than primaquine against hepatic stages of Plasmodium berghei, although this was accompanied by cytotoxic effects on Huh-7 hepatocytes. Relevantly, the conjugates displayed nanomolar activities against blood stage P. falciparum parasites, with no evidence of hemolytic effects below 100 µM. Moreover, the new compounds were at least 25-fold more potent than primaquine against P. falciparum gametocytes. Thus, the new antiplasmodial hits disclosed herein emerge as valuable templates for the development of multi-stage antiplasmodial drug candidates.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cinamatos
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Malária Falciparum
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Antimaláricos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article