Synthesis and Evaluation of Antimalarial Activity of Oxygenated 3-alkylpyridine Marine Alkaloid Analogues

• Published in: Chemical biology & drug design 2011-09, Vol.78 (3), p.477-482
• Main Authors: Hilário, Flaviane F., de Paula, Renata Cristina, Silveira, Mariana L. T., Viana, Gustavo H. R., Alves, Rosemeire B., Pereira, Juliana R. C. S., Silva, Luciana Maria, de Freitas, Rossimiriam P., de Pilla Varotti, Fernando
• Format: Article
• Language: English
• Subjects: 3-alkylpyridines; Alkaloids - chemical synthesis; Alkaloids - chemistry; Alkaloids - pharmacology; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Cell Line; Cell Survival - drug effects; Humans; malaria; Malaria, Falciparum - drug therapy; marine alkaloids; Plasmodium falciparum - drug effects; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Structure-Activity Relationship
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2011.01154.x

A series of new oxygenated analogues of marine 3‐alkylpyridine alkaloids were prepared from 3‐pyridinepropanol in few steps and in good yields. The key step for the synthesis of these compounds was a Williamson etherification under phase‐transfer conditions. All new compounds were evaluated for their antiplasmodial activity and cytotoxicity. A significant reduction in parasitaemia was observed for some of the prepared compounds, and the majority of them exhibited a selectivity index (SI) ranging from 2.78 to 15.58, which suggests that these compounds may be a promising class of substances with antimalarial activity. A series of new oxygenated analogues of marine 3‐alkylpyridine alkaloids were prepared from 3‐pyridinepropanol in few steps and in good yields. All new compounds were evaluated for their antiplasmodial activity and cytotoxicity. A significant reduction in parasitemia was observed for some of the prepared compounds and the majority of them exibited a selectivity index (SI) ranging from 2.78 to 15.58, which suggests that these compounds may be a promising class of substances with antimalarial activity.