Research Background: Discovery and Evaluation of Synthetic Diterpenes

My scientific work began more than two decades ago, when I hypothesised that the traditional extraction methods used by Andean friars to prepare medicinal extracts from Espeletia species (commonly known as frailejón) likely involved oxidative transformations. During these artisanal procedures, the most abundant natural diterpene appears to undergo a rearrangement, giving rise to a more stable molecular structure that I designated Compound 1.

Building on this insight, I successfully obtained synthetic diterpene 1 from (−)-kaura‑9(11),16‑dien‑19‑oic acid, a kaurane diterpene isolated from Venezuelan Espeletia species. Using the oxidative methodology developed under the guidance of my mentor, Dr. Tatsuhiko Nakano, I generated Compound 1 and submitted it for biological evaluation through the NCI/NIH Developmental Therapeutics Program, which enabled testing across 60 human cancer cell lines.

Key Findings and Biological Activity

Compound 1

• Activity profile: Demonstrated potent cytostatic and cytotoxic effects across multiple tumour cell lines in the NCI’s 60‑cell panel.
• Growth inhibition: Achieved a GI₅₀ of 51.6 nM against the CNS cancer cell line SF‑539, indicating strong antiproliferative activity.
• Cytotoxicity metrics: Showed an LC₅₀ of 100 μM, with a log₁₀ GI₅₀ value of −7.29, reflecting a high level of biological potency at nanomolar concentrations.

These results provided early evidence that oxidative derivatives of Espeletia diterpenes may possess significant anticancer potential, supporting further exploration of their mechanism of action and structure–activity relationships.