Antileishmanial activity and ultrastructural changes of sesquiterpene lactones isolated from Calea pinnatifida (Asteraceae)

• Published in: Bioorganic chemistry 2019-03, Vol.83, p.348-353
• Main Authors: Caldas, Lhaís Araújo, Yoshinaga, Meire L., Ferreira, Marcelo J.P., Lago, João H.G., de Souza, Adriana B., Laurenti, Márcia D., Passero, Luiz Felipe. D., Sartorelli, Patricia
• Format: Article
• Language: English
• Subjects: Animals; Antileishmanial activity; Asteraceae - chemistry; Calea pinnatifida; Lactones - chemical synthesis; Lactones - pharmacology; Leishmania mexicana - drug effects; Leishmania mexicana - ultrastructure; Membrane Potential, Mitochondrial - drug effects; Mitochondrial membrane potential; Sesquiterpene lactones; Sesquiterpenes - chemical synthesis; Sesquiterpenes - pharmacology; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Ultrastructural changes
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2018.10.059

[Display omitted] •Fractionation of C. pinnatifida isolated calein C (1) and calealactone C (2).•It is the first reported occurrence of (1) and (2) in Calea pinnatifida.•(1) and (2) showed potential against promastigotes of L. amazonensis.•(2) decreased the mitochondrial membrane potential of L. amazonensis. Bioactivity-guided fractionation of antileishmanial active CH2Cl2 phase of MeOH extract from leaves of Calea pinnatifida led to isolation of two sesquiterpene lactones calein C (1) and calealactone C (2), which structures were stablished on the basis of spectroscopic analysis. Compounds 1 and 2 displayed potent activity against Leishmania amazonensis promastigotes with EC50 of 1.7 and 4.6 µg mL−1, respectively. Compound 2 presented low cytotoxicity for J774 macrophages and displayed activity against amastigote forms of L. amazonensis similar to miltefosine with CC50 values of 31.73 and 27.18 µg mL−1, respectively. Additionally, compounds 1 and 2 caused ultrastructural changes in promastigotes leading to a loss of their classical structural morphology, as evidenced by electron microscopy. Also compound 2 decreased the mitochondria membrane potential. To the best of our knowledge, this is the first occurrence of 1 and 2 in C. pinnatifida. The results obtained highlighted the importance of studying sesquiterpene lactones isolated from Calea pinnatifida in terms of antileishmanial activity, in order to understand the mechanism of action of the isolated compounds in promastigotes forms of L. amazonensis.