Selective cytotoxicity of ent-kaurene diterpenoids isolated from Baccharis lateralis and Baccharis retusa (Asteraceae)

Author(s)

Silva, Matheus L. ; Oliveira, Cyntia S. ; dos Santos, Wagner J. O. ; Oliveira Junior, Vani X. ; Antar, Guilherme M. ; Lago, Joao H. G. ; Cerchiaro, Giselle

• Document type: Journal article
• Source: ARCHIV DER PHARMAZIE; v. N/A, p. 7-pg., 2022-05-12.

Abstract

This study presents the cytotoxic activity evaluation of the natural diterpenes ent-kaurenoic acid (1) and its 15 beta-hydroxy (2), 15 beta-senecioyloxy (3), and 15 beta-tiglinoyloxy (4) derivatives, isolated from Brazilian native plants, Baccharis retusa and B. lateralis (Asteraceae). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay, it was observed that compound 1 displayed in vitro activity towards the aggressive MDA-MB-231 adenocarcinoma cell line and reduced toxicity against MCF-10A nontumorigenic epithelial cells, indicating expressive selectivity. On the contrary, compounds 2-4 exhibited reduced toxicity and selectivity in both tested cell lines. Based on the chemical structures of compounds 1-4, it is suggested that the presence of additional functional groups at the C-15 position-a hydroxyl group in compound 2 and isomeric isoprene units in compounds 3 and 4-might be responsible for the reduction in the potential/selectivity. In silico studies show, for compounds 1-4, good predictions regarding bioavailability and ADME (absorption, distribution, metabolism, and excretion) properties as well as no alerts for PAINS (pan-assay structures interference). In conclusion, ent-kaurenoic acid (1), a common diterpenoid isolated in high amounts from different plants belonging to the Baccharis genus, has been shown to be a promising cytotoxic agent against an aggressive adenocarcinoma cell line (MDA-MB-23) and, if well exploited, could be used as a scaffold in the development of molecular prototypes for the treatment of breast cancer. (AU)

• FAPESP's process: 21/02789-7 - Search for bioactive metabolites with antiparasitic action in plant species from Atlantic Forest and Cerrado regions - a chemical, phenotypical, and metabolomic approach
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• FAPESP's process: 20/14175-0 - Studies of the anticancer action and mechanism of new copper complexes using natural products ligands
• Grantee: Giselle Cerchiaro
• Support Opportunities: Regular Research Grants