Document Detail

Synthesis and antiplasmodial activity of betulinic Acid and ursolic Acid analogues.
MedLine Citation:
PMID:  23085651     Owner:  NLM     Status:  In-Data-Review    
More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC(50) = 220 and 175 nM, respectively) while 1a and b demonstrated good activity (IC(50) = 4 and 5 μM, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC(50 )of 4 μM and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s).
Adrine M Innocente; Gloria N S Silva; Laura Nogueira Cruz; Miriam S Moraes; Myna Nakabashi; Pascal Sonnet; Grace Gosmann; Célia R S Garcia; Simone C B Gnoatto
Publication Detail:
Type:  Journal Article     Date:  2012-10-12
Journal Detail:
Title:  Molecules (Basel, Switzerland)     Volume:  17     ISSN:  1420-3049     ISO Abbreviation:  Molecules     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100964009     Medline TA:  Molecules     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  12003-14     Citation Subset:  IM    
Laboratório de Fitoquímica e Síntese Orgânica, Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul. Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil.
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