N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Gomes, A (Author) Other; Perez, B (Author) Other; Albuquerque, I (Author) Other; Machado, M (Author) Other; Prudencio, M (Author) Other; Nogueira, F (Author) Other; Teixeira, C (Author) Other; Gomes, P (Author) FCUP

Journal

Title: ChemMedChem

ISSN: 1860-7179

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 23 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-009-2GB

DOI: 10.1002/cmdc.201300459

Abstract (EN): Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported. The compounds were found to be highly potent against both blood-stage P.falciparum, chloroquine-sensitive 3D7 (IC50=17.0-39.0nM) and chloroquine-resistant W2 and Dd2 strains (IC50=3.2-41.2 and 27.1-131.0nM, respectively), and liver-stage P.berghei (IC50=1.6-4.9¿M) parasites. These findings bring new hope for the possible future "rise of a fallen angel" in antimalarial chemotherapy, with a potential resurgence of quinacrine-related compounds as dual-stage antimalarial leads. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Language: English

Type (Professor's evaluation): Scientific