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

Abstract

This study presents the cytotoxic activity evaluation of the natural diterpenes ent-kaurenoic acid (1) and its 15β-hydroxy (2), 15β-senecioyloxy (3), and 15β-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.

• Authors: Matheus L Silva, Cyntia S Oliveira, Wagner J O Dos Santos, Vani X Oliveira Junior, Guilherme M Antar, João H G Lago, Giselle Cerchiaro
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 355 Issue 8 Pg. e2200083 (Aug 2022) ISSN: 1521-4184 [Electronic] Germany
• PMID: 35556256 (Publication Type: Journal Article)
• Copyright: © 2022 Deutsche Pharmazeutische Gesellschaft.

Chemical References

• Antineoplastic Agents
• Diterpenes
• Diterpenes, Kaurane

Topics

• Adenocarcinoma
• Antineoplastic Agents (chemistry)
• Baccharis (chemistry)
• Diterpenes (pharmacology)
• Diterpenes, Kaurane (chemistry)
• Humans
• Structure-Activity Relationship