Highly selective alkylcoumarates and diterpenoids isolated from leaves of Baccharis quitensis: a search for new hit compounds against Trypanosoma cruzi

Author(s)

Peres, Nathalia ; Silva, Matheus L. ; Ueno, Anderson K. ; Antar, Guilherme M. ; Levatti, Erica V. C. ; Tempone, Andre G. ; Lago, Joao Henrique G.

• Document type: Journal article
• Source: NATURAL PRODUCT RESEARCH; v. N/A, p. 7-pg., 2024-03-25.

Abstract

In the present work, the hexane extract of aerial parts of Baccharis quitensis Kunth. was subjected to chromatographic fractionation to afford two alkyl phenylpropanoids: n-docosyl (E)-p-coumarate (1) and n-tetracosyl (E)-p-coumarate (2) as well as five diterpenes: ent-kaurenoic acid (3), grandifloric acid (4), 15 beta-senecioyl-oxy-ent-kaur-16-en-19-oic acid (5), and 15-oxo-ent-kaurenoic acid (6). Using an ex-vivo assay with macrophages infected with Trypanosoma cruzi, compounds 1 and 2 demonstrated high potency against intracellular amastigotes, with EC50 values of 7.5 and 6.9 mu M, respectively. Compound 6 revealed a moderate potency against T. cruzi, with an EC50 of 25.6 mu M, and compounds 3-5 showed no effectiveness. Additionally, compounds 1-6 compounds presented no toxicity for mammalian cells to the highest tested concentration of 200 mu M. Based on potency and the selectivity indexes of 1, 2 and 6, these compounds could be future candidates for optimisation studies for the design of prototypes against Chagas disease. (AU)

• FAPESP's process: 21/04464-8 - Microbial and plant prototypes as drug candidates for protozoan neglected diseases and multidrug-resistant bacteria
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/12447-1 - Searching for specialized metabolites from Brazilian floristic biodiversity as drug candidates for neglected tropical diseases
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants