Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity

Author(s)

Aguiar, Anna C. C. ^[1] ; Murce, Erika ^[2] ; Cortopassi, Wilian A. ^[3] ; Pimentel, Andre S. ^[2] ; Almeida, Maria M. F. S. ^[4] ; Barros, Daniele C. S. ^[4] ; Guedes, Jessica S. ^[4] ; Meneghetti, Mario R. ^[4] ; Krettli, Antoniana U. ^[1]

Affiliation

^[1] Ctr Pesquisas Rene Rachou Fiocruz, Lab Malaria, Belo Horizonte, MG - Brazil

^[2] Pontifical Catholic Univ Rio de Janeiro, Dept Chem, Rio De Janeiro - Brazil

^[3] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 - USA

^[4] Univ Fed Alagoas, Inst Quim & Biotecnol, Maceio - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE; v. 8, n. 3, p. 459-464, DEC 2018.
• Web of Science Citations: 1

Abstract

In spite of recent efforts to eradicate malaria in the world, this parasitic disease is still considered a major public health problem, with a total of 216 million cases of malaria and 445,000 deaths in 2016. Artemisinin-based combination therapies remain effective in most parts of the world, but recent cases of resistance in Southeast Asia have urged for novel approaches to treat malaria caused by Plasmodium falciparum. In this work, we present chloroquine analogs that exhibited high activity against sensitive and chloroquine-resistant P. falciparum blood parasites and were also active against P. berghei infected mice. Among the compounds tested, DAQ, a chloroquine analog with a more linear side chain, was shown to be the most active in vitro and in vivo, with low cytotoxicity, and therefore may serve as the basis for the development of more effective chloroquine analogs to aid malaria eradication. (AU)

• FAPESP's process: 14/50983-3 - INCT 2014: complex fluids
• Grantee: Antonio Martins Figueiredo Neto
• Support Opportunities: Research Projects - Thematic Grants