In Vitro Leishmanicidal Activities of Sesquiterpene Lactones from Tithonia diversifolia against Leishmania braziliensis Promastigotes and Amastigotes

Author(s)

de Toledo, Juliano S. ^[1] ; Ambrosio, Sergio R. ^{[2, 3]} ; Borges, Carly H. G. ^[3] ; Manfrim, Viviane ^[1] ; Cerri, Daniel G. ^[1] ; Cruz, Angela K. ^[1] ; Da Costa, Fernando B. ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cell Biol Mol & Pathogen Bioagents, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, AsterBioChem Res Team, Lab Pharmacognosy, Dept Pharmaceut Sci, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Franca UNIFRAN, Ctr Res Exact & Technol Sci, BR-14404600 Franca, SP - Brazil

• Document type: Journal article
• Source: Molecules; v. 19, n. 5, p. 6070-6079, MAY 2014.
• Web of Science Citations: 17

Abstract

Natural compounds represent a rich and promising source of novel, biologically active chemical entities for treating leishmaniasis. Sesquiterpene lactones are a recognized class of terpenoids with a wide spectrum of biological activities, including activity against Leishmania spp. In this work, a sesquiterpene lactone-rich preparation-a leaf rinse extract (LRE) from Tithonia diversifolia-was tested against promastigote forms of L. braziliensis. The results revealed that the LRE is a rich source of potent leishmanicidal compounds, with an LD50 value 1.5 +/- 0.50 mu g.mL(-1). Therefore, eight sesquiterpene lactones from the LRE were initially investigated against promastigote forms of L. braziliensis. One of them did not present any significant leishmanicidal effect (LD50 > 50 mu g.mL(-1)). Another had a cytotoxic effect against macrophages (4.5 mu g.mL(-1)). The five leishmanicidal compounds with the highest level of selectivity were further evaluated against intracellular parasites (amastigotes) using peritoneal macrophages. Tirotundin 3-O-methyl ether, tagitinin F, and a guaianolide reduced the internalization of parasites after 48 h, in comparison with the negative control. This is the first report on sesquiterpene lactones that have potent leishmanicidal effects on both developmental stages of L. braziliensis. (AU)

• FAPESP's process: 06/07308-7 - Constituents of tithonia diversifolia, chemical profile and seasonal variation in glandular trichomes content and herbivory of chlosyne lacinia on the leaves.
• Grantee: Fernando Batista da Costa
• Support Opportunities: Research Grants - Meeting - Abroad
• FAPESP's process: 06/50323-7 - Control of gene expression and genetlc plasticity in Leishmania
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants