Diterpenes and New Antifungal Epimers Derived From Grindelia puberula Hook & Arn. In Vitro and In Silico Studies
Year: 2025
Type: article
Abstract: ABSTRACT Two new labdane diterpenes, (4S,5R,10S,13S)‐19‐acetoxy‐7‐oxo‐labd‐8(9)‐en‐15‐oic acid‐15‐methyl ester (1) and (4R,5R,10S,13S)‐19‐acetoxy‐7‐oxo‐labd‐8(9)‐en‐15‐oic acid‐15‐methyl ester (2), along with two methyl ester derivatives of the known acid compounds, (4R,5S,9S,10R,13S)‐ent‐7‐labden‐17‐acetoxy‐18‐hydroxy‐15‐oic acid (3), and (3R,5S,9S,10S,13S)‐ent‐7‐labden‐17‐acetoxy‐3‐α‐hydroxy‐15‐oic acid (4), were obtained from Grindelia puberula Hook & Arn, collected in northern Argentina. Their structures and absolute configurations were elucidated based on one‐ and two‐dimensional nuclear magnetic resonance spectroscopy, mass spectrometry, and circular dichroism analysis. The CHCl3 sub‐extract obtained from the aerial parts of this species, along with the pure compounds, were evaluated for antifungal activity against Botrytis cinerea, a widespread necrotrophic fungal pathogen responsible for significant economic losses worldwide. Among the tested compounds, 2 (IC50 = 27.7 ± 3.8 µg/mL) exhibited the highest antifungal activity, demonstrating greater efficacy compared to its C‐4 epimer. Furthermore, an in silico structure‐activity relationship study was conducted. Molecular docking simulations revealed that compound 2 displayed the highest binding affinity to the B. cinerea cytochrome b complex (–9.62 kcal/mol), a key target in antifungal therapy.
Source: Chemistry & Biodiversity
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4409234576