Synthesis, in vitro Antimalarial Activity and in silico Studies of Hybrid Kauranoid 1,2,3-Triazoles Derived from Naturally Occurring Diterpenes

• Autor(a) principal: Santos,Juliana de O.
• Data de Publicação: 2016
• Outros Autores: Pereira,Guilherme R., Brandão,Geraldo C., Borgati,Tatiane F., Arantes,Lucas M., Paula,Renata C. de, Soares,Luciana F., Nascimento,Maria F. A. do, Ferreira,Márlia R. C., Taranto,Alex G., Varotti,Fernando P., Oliveira,Alaíde B. de
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000300551
• topic: kaurenoic acid; xylopic acid; click chemistry; antiplasmodial activity; PfATP6 inhibitors

We herein report the synthesis of hybrid kauranoid molecules of type 1,2,3-triazole-1,4-disubstituted aiming to improve the antimalarial activity of kaurenoic and xylopic acids. The CuI-catalyzed cycloaddition of azides and kauranoid terminal alkynes was explored as a hybridization strategy. Kauranoid terminal alkynes were prepared from kaurenoic and xylopic acids that were isolated from Wedelia paludosa D. C. (Asteraceae) and Xylopia frutescens Aubl. (Annonaceae). A total of 15 kauranoid derivatives, including nine new triazoles, were obtained and five out of these were more active than the original diterpenes. Interestingly, an increased activity was observed for a kauranoid propargyl ether. Interaction between ent-kaurane diterpene derivatives and Ca2+-ATPase (PfATP6) was investigated. Synthesis of diterpene derivatives emerges as a possible route to be explored in the quest of potentially new inhibitors of PfATP6.