Malária: aspectos históricos e quimioterapia

Malária: Dos velhos fármacos aos novos alvos moleculares

“…Devido ao aumento de cepas P. falciparum cloroquina-resistentes (CQR), foram sintetizados novos antimaláricos derivados da cloroquina como, por exemplo, a amodiaquina e a mefloquina, as quais possuem a mesma ação esquizonticida da cloroquina (KROGSTAD et al, 1992). No entanto, a cloroquina ainda é a substância de escolha para tratamento em alguns países, principalmente para tratar infecções por P. vivax em áreas nas quais esse fármaco ainda é eficaz (AGUIAR et al, 2012;FRANÇA;KITCHENER;NASVELD;EDSTEIN, 2007;WELLS et al, 2009). No entanto, em áreas com P. vivax CQR, terapias baseadas em artemisinina precisam ser adotadas (AGUIAR et al, 2012;BUTCHER, 1997 (AGUIAR et al, 2012;ARAUJO et al, 2008;LUZHKOV et al, 2007;MUGNAINI et al, 2007;ROSENTHAL, 2003).…”

“…Os fármacos utilizados atualmente contra a malária não permitem cura, muitas vezes há recidivas da doença, além de serem muito tóxicos, de difícil aplicação e eficácia insatisfatória, fazendo com que vários pacientes desistam do tratamento (ARAÚJO et al, 2008;DONDORP et al, 2009;FRANÇA et al, 2008). Portanto, é necessário encontrar novas alternativas terapêuticas para melhorar a quimioterapia existente contra a malária, devido ao grande número de pessoas acometidas.…”

Synthesis by Click Reactions and Antiplasmodial Activity of Lupeol 1,2,3-Triazole Derivatives

“…3 Plants are still used in the endemic countries as remedies to treat a range of diseases, including malaria 3 and afforded important antimalarial drugs, such as quinine (1), an alkaloid that was isolated in 1820 from barks of Peruvian Cinchona species (Rubiaceae) and was widely used until after the Second World War. Quinine was a template for the synthesis of chloroquine (2), in 1940, a quinoline that was widely used in malaria therapeutics 4 resulting in Plasmodium falciparum resistance, in the 1960s. New antimalarial drugs have been developed such as primaquine (3), mefloquine (4), lumefantrine (5) and amodiaquine (6) (Figure 1).…”

“…New antimalarial drugs have been developed such as primaquine (3), mefloquine (4), lumefantrine (5) and amodiaquine (6) (Figure 1). 1,4 Artemisinin (7), an antimalarial sesquiterpene lactone containing an endoperoxide bridge, was isolated in China from Artemisia annua L., and its semi-synthetic Vol. 28, No.…”

“…9 Several NP such as alkaloids, disclose relevant biological activities, 12 as can be highlighted by the quinoline derivatives (quinine) of known antimalarial activity. 4 In this context the introduction of nitrogenated moieties in non-alkaloids NP, such as 1,2,3-triazole rings is a good strategy to obtain more active compounds. 13,14 In addition, the 1,2,3-triazole ring is exclusively synthetic and may be used for coupling between two or more molecules of interest aiming to improve their pharmacological and pharmacokinetic characteristics.…”