Insignoic acids A - E, unusual α, β-unsaturated keto fatty acids isolated from the exocarp of Australian rainforest tree Endiandra insignis (Lauraceae)

Ritesh Raju; Paayal Kumar; Paul Reddell; Jason Cullen; David Harman; Alan T Maccarone; Celine Kelso; Gerald Muench

doi:10.1016/j.fitote.2023.105815

Insignoic acids A - E, unusual α, β-unsaturated keto fatty acids isolated from the exocarp of Australian rainforest tree Endiandra insignis (Lauraceae)

Fitoterapia. 2024 Mar:173:105815. doi: 10.1016/j.fitote.2023.105815. Epub 2023 Dec 31.

Authors

Ritesh Raju¹, Paayal Kumar², Paul Reddell³, Jason Cullen⁴, David Harman⁵, Alan T Maccarone⁶, Celine Kelso⁶, Gerald Muench⁷

Affiliations

¹ Department of Pharmacology, Western Sydney University, Campbelltown Campus, Sydney, Australia. Electronic address: r.raju@westernsydney.edu.au.
² Department of Pharmacology, Western Sydney University, Campbelltown Campus, Sydney, Australia.
³ QBiotics Ltd, PO Box 1, Yungaburra, Queensland, Australia.
⁴ QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
⁵ Department of Physical Science, Western Sydney University, Campbelltown Campus, Sydney, Australia.
⁶ Molecular Horizons, University of Wollongong, Wollongong, Australia; School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.
⁷ Department of Pharmacology, Western Sydney University, Campbelltown Campus, Sydney, Australia; NICM Health Research Institute, Western Sydney University, Westmead, Australia.

PMID: 38168569
DOI: 10.1016/j.fitote.2023.105815

Abstract

Anti-inflammatory bioassay-guided compound isolation from the exocarp of the Australian rainforest tree Endiandra insignis (family Lauraceae) has led to the discovery and structural elucidation of unusual α, β-unsaturated twenty-four carbon fatty acids and their positional isomers, insignoic acids A - E (1a - 5c). The stereochemistry and position of the double bond within the aliphatic chain were independently determined via NMR spectroscopy and Ozone-Induced Dissociation (OzID) Mass Spectrometry, respectively. Compounds (1a - 5c) displayed good to moderate anti-inflammatory activity in the range of 8-84 μM. The low therapeutic index observed when assessing the cell viability in the RAW macrophage cell lines, prompted us to investigate the anticancer potential of these unusual fatty acids. The anti-cancer activity was assessed in A-431 carinoma cell lines and MM649 melanoma cell lines. Insignoic acid C (3a-f) exhibited the highest level of potency with an IC₅₀ value of 5-7 μM against both the cell lines. The insignoic acids are the first of their kind known for incorporating an alpha-beta unsaturated system flanked next to a keto group with an additional level of oxygenation at C-6 in a 24‑carbon fatty acid backbone.

Keywords: Anti-cancer; Anti-inflammatory; Insignoic acids; Ozonolysis; Unsaturated fatty acids.

MeSH terms

Anti-Inflammatory Agents
Australia
Carbon
Fatty Acids
Fatty Acids, Unsaturated
Lauraceae*
Molecular Structure
Rainforest
Trees*

Substances

Fatty Acids, Unsaturated
Fatty Acids
Anti-Inflammatory Agents
Carbon