4, 9‐Diaminoacridines and 4‐Aminoacridines as Dual‐Stage Antiplasmodial Hits. (7th December 2020)

• Record Type: Journal Article
• Authors: Fonte, Mélanie; Tassi, Natália; Fontinha, Diana; Bouzón‐Arnáiz, Inés; Ferraz, Ricardo; Araújo, Maria J.; Fernàndez‐Busquets, Xavier; Prudêncio, Miguel; Gomes, Paula; Teixeira, Cátia
• Is Part Of: ChemMedChem. Volume 16:Number 5(2021)
• Page Start: 788
• Page End: 792
• Publication Date: 2020-12-07
• Subjects: acridines -- antimalarial activity -- blood-stage -- liver-stage -- malaria -- Plasmodium -- synthesis; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000740
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Multi‐stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine‐based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine‐sensitive and ‐resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual‐stage antiplasmodial hits. Abstract : Two‐in‐one : We disclose two novel acridine‐based families of compounds that combine the structural features of primaquine and chloroquine. The compounds retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine‐sensitive and ‐resistant P. falciparum strains, and against the hepatic stages of P. berghei, hence acting as dual‐stage antiplasmodial hits.