Grindelia ventanensis (Asteraceae) is an endemic species growing wildly in Sierra de la Ventana, southwest of Buenos Aires province, Argentina. Grindelia species, are characterized by the production of bicyclic labdane-type diterpenoids.

In a previous study we reported the cholinesterase inhibition observed for the ethanolic extract of G. ventanensis and the isolation of an active metabolite, 17-hydroxycativic acid, which showed antioxidant activity and moderate acetylcholinesterase (AChE) inhibition, without cytotoxic activity [1]. In this work, we focused our attention on the dichloromethane (DCM) extract of this plant, and its components, looking forward to identify other bioactive cativic acid analogs.

DCM extract showed strong antioxidant activity (IC₅₀ = 27.03 μg/mL) detected by the reduction of DPPH and good AChE inhibition (IC₅₀ =121.9 µg/mL). Then, this extract was fractionated by column chromatography and HPLC. Six diterpenoids were isolated and identified as 13-methyl-17-oxo-labda-7,13-diene-15-oic acid (1), 17-hydroxy-13-methyl-labda-7,13-diene-15-oic acid, 18-acetoxy-17-hydroxy cativic acid, 17-acetoxycativic acid, cativic acid and grindelic acid. These compounds were identified by RMN and MS analysis.

All the isolated diterpenoids were evaluated as AChE inhibitors and radical scavengers.

Compound 1 elicited the best results in both bioassays, with IC₅₀ = 11.04 µM in the AChE inhibition test and an antioxidant activity comparable to trolox, the reference antioxidant (IC₅₀ = 7.13 µM). Significant bioactivity was also observed for the rest of the isolated compounds.

These results suggest that G. ventanensis could be a source of bioactive compounds that may be of interest for the development of potential new alternatives in the treatment of Alzheimer's disease.