N-Cinnamoylated Chloroquine Analogues as Dual-Stage Antimalarial Leads

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

Authors

Bianca C Perez (Author) Other; Catia Teixeira (Author) Other; Ines S Albuquerque (Author) Other; Jiri Gut (Author) Other; Philip J Rosenthal (Author) Other; Jose R B Gomes (Author) Other; Miguel Prudencio (Author) Other; Paula Gomes (Author) FCUP

Journal

Title: Journal of Medicinal Chemistry

Vol. 56

Pages: 556-567

ISSN: 0022-2623

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 64 Citations

Scopus - 63 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-15Z

DOI: 10.1021/jm301654b

Abstract (EN): The control of malaria is challenged by drug resistance, and new antimalarial drugs are needed. New drug discovery efforts include consideration of hybrid compounds as potential multitarget antimalarials. Previous work from our group has demonstrated that hybrid structures resulting from cinnamic acid conjugation with heterocyclic moieties from well-known antimalarials present improved antimalarial activity. Now, we report the synthesis and SAR analysis of an expanded series of cinnamic acid derivatives displaying remarkably high activities against both blood- and liver-stage malaria parasites. Two compounds judged most promising, based on their in vitro activity and druglikeness according to the Lipinski rules and Veber filter, were active in vivo against blood-stage rodent malaria parasites. Therefore, the compounds reported represent a new entry as promising dual-stage antimalarial leads.

Language: English

Type (Professor's evaluation): Scientific