Definition of an electronic profile of compounds with inhibitory activity against hematin aggregation in malaria parasite

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Portela, C (Author) Other; Afonso, CMM (Author) FFUP; Pinta, MMM (Author) FFUP; Ramos, MJ (Author) FCUP

Journal

Title: Bioorganic and Medicinal Chemistry

Vol. 12

Pages: 3313-3321

ISSN: 0968-0896

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 64 Citations

Scopus - 67 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-9Y7

DOI: 10.1016/j.bmc.2004.03.060

Abstract (EN): Malaria is one of the most important parasitic diseases, affecting almost half of the world and posing a threat to the other half. Xanthone derivatives can behave as antimalarial drugs in the same mechanistic way as chloroquine and other related quinolines. This action is due to the inhibition of the detoxification pathway of the parasite, responsible for the production of hemozoin. We report a study of the electronic properties of the xanthonic and quinolinic compounds based on DFT calculations, in order to determine a pattern that could be applied to the development of new potentially active antimalarial molecules. As a result, a new interpretation of structure-activity relationship of the quinoline antimalarial drugs, and of the active hydroxylated xanthones is proposed here. We conclude that electronic features rather than steric factors control primarily the inhibitory activity of the studied compounds against hematin aggregation, concurring to a potential antimalarial activity. 2004 Elsevier Ltd. All rights reserved.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9