Enhancing Bioactivities and Chemical Properties of A Marine Briarane-type Diterpenoid With Late-Stage Diversification

07 June 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Excavatolide B (1, ExcB), a briarane-type diterpenoid isolated from Formosan gorgonian Briareum stechei, exhibits promising anti-inflammatory activity with low cytotoxicity. In this study, we report the structure-activity relationship of ExcB derivatives with late-stage modifications around the carboframe of 1. We identified a potent analog 22 with improved in vitro inhibitory activities against the inducible nitric oxide synthase gene expression, nitric oxide production, IL-6, and TNF- production in LPS-stimulated RAW264.7 macrophages. The esterification of piperidyl with proper spacer length in analog 22 also substantially increased the aqueous solubility >100-fold. More importantly, under similar dosing regimen compared to that of parent 1, 22 in its salt form showed an 80% increase in anti-inflammatory activity to alleviate carrageenan-induced paw edema in rats. Overall, these findings would greatly facilitate the further development of more potent analogs with enhanced bioactivities and improved drug-like properties of the underexplored class of briarane-type natural diterpenoids.


Marine Briarane-type Diterpene
Excavatolide B
Late-stage diversification

Supplementary materials

Enhancing Bioactivities and Chemical Properties of A Marine Briarane-type Diterpenoid with Late-Stage Diversification
Water Solubility of compound 1, 22 and 22-HCl by HPLC method; X-ray crystallographic analysis; 1H and 13C NMR spectra; and HRMS spectra.


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