Anais da Academia Brasileira de Ciências (2009) 81(4): 715-740 (Annals of the Brazilian Academy of Sciences) ISSN 0001-3765 www.scielo.br/aabc Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids ALAÍDE B. OLIVEIRA 1 , MARIA FÂNI DOLABELA 1,2 , FERNÃO C. BRAGA 1 , ROSE L.R.P. JÁCOME 1 , FERNANDO P. VAROTTI 1 and MARINETE M. PÓVOA 3 1 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6.627, 31270-901 Belo Horizonte, MG, Brasil 2 Faculdade de Farmácia, ICS, Universidade Federal do Pará, 68075-110 Belém, PA, Brasil 3 Laboratório de Malária, Seção de Parasitologia, Instituto Evandro Chagas, BR-316, km 7 s/n, B. Levilândia, 67030-000 Ananindeua, PA, Brasil Manuscript received on January 13, 2009; accepted for publication on July 9, 2009; contributed by ALAÍDE B. OLIVEIRA* ABSTRACT Malaria remains one of the most serious world health problem and the major cause of mortality and morbidity in the endemic regions. Brazil is among the 30 high-burden countries and most of the cases occur in the Legal Amazonian Region. New chemotherapeutical agents are needed for the treatment of malaria. Many plant species are used in traditional medicines of malarious countries and a relatively few number of these have been investigated for evaluation of their antimalarial effect. Still lower is the number of those that have had the active natural compounds isolated and the toxicity determined. This area is, then, of great research interest. A discovery project of antimalarial natural products from plants traditionally used to treat malaria must include in vitro and in vivo assays as well as bioguided isolation of active compounds. The final products would be antimalarial chemical entities, potential new drugs or templates for new drugs development, and/or standardized antimalarial extracts which are required for pre-clinical and clinical studies when the aim is the development of effective and safe phythomedicines. This review discusses these two approaches, presents briefly the screening methodologies for evaluation of antimalarial activity and focuses the activity of alkaloids belonging to different structural classes as well as its importance as new antimalarial drugs or leads and chemical markers for phytomedicines. Key words: natural products, alkaloids, antimalarial activity, medicinal plants, phytomedicines. INTRODUCTION Malaria remains one of the most prevalent infectious disease in the world. In 2006, there were approximately 247 million cases of malaria and 3.3 billion people that were at risk of the disease. Nearly 1 million deaths, mostly of children under the age of 5, were caused by malaria. There are currently 109 malarious countries and territories, of which 45 are within the World Health Organization (WHO) African region (WHO 2008). *Member Academia Brasileira de Ciências Correspondence to: Alaíde Braga de Oliveira E-mail: alaidebraga@terra.com.br Although malaria is a curable and preventable dis- ease, its prevalence increased in the 1980s and 1990s as the parasites developed resistance to the most fre- quently used antimalarial drugs and the vectors became resistant to insecticides. During the 1990s, child deaths caused by malaria increased by up to two-fold in some parts of sub-Saharan Africa. The disease also re-emer- ged in several countries in Central Asia, Eastern Eu- rope and South-East Asia. The majority of the cases for 2006 were estimated in Africa (86%), followed by South-East Asia (9 %) and Eastern Mediterranean re- gions (3%) (Fig. 1). An Acad Bras Cienc (2009) 81 (4)