Antiplasmodials soulattrolide derivatives from Calophyllum brasiliense and its mechanism of activity

Abstract

Parasitic diseases such as malaria, leishmaniasis, trypanosomia-sis, and schistosomiasis are just one of the main causes of diseaseand death in the world today (WHO, 2016). In 2016, 91 countriesreported a total of 216 million cases of malaria, which representsan increase to 5 million cases in relation to the previous year, with15 countries holding 80% of the global burden of malaria. The totalnumber of deaths worldwide reached 445.000, similar to thatreported in 2015 (WHO, 2017; Chin, 2001; Newman et al., 2016),so there is an urgent need to discover new, safe and effective drugsfor the prophylaxis and treatment of malaria, mainly due to thedevelopment of resistance ofPlasmodium falciparum, the mostlethal Plasmodium species to chloroquine and other antimalarialdrugs. Few alternative drugs are in development and urgent mea-sures are needed to identify new types of antimalarial agents,many of which have originated from natural products (Olumese,2015; Leach, 2001).Clusiaceaeis one of the families of plants inwhich compounds with antimalarial activity have been found, suchas xanthones and derivatives of acylphloroglucinol. Since the genusCalophyllumis a potential source of secondary metabolites and itsspecies are little explored in the field of malaria, their explorationis justified as a phytotherapeutic alternative in the treatment ofmalaria (Hay et al., 2004; Chanphen et al., 1998; Pierson et al., 2010; Guillaume et al., 2009). This paper reports the isolation ofsoulattrolide (1) fromC. brasiliense. the preparation of eight newderivatives (2–9) by hemi-synthesis and the bioactivity studiesthereof.