np0c00313_si_001.pdf (3.17 MB)
Hydroxy-neo-Clerodanes and 5,10-seco-neo-Clerodanes from Salvia decora
journal contribution
posted on 2020-06-29, 13:39 authored by José Rivera-Chávez, Celia Bustos-Brito, Enrique Aguilar-Ramírez, Diego Martínez-Otero, Luis D. Rosales-Vázquez, Alejandro Dorazco-González, Patricia Cano-SánchezPreliminary analysis of the mass
spectrometric (MS) and NMR spectroscopic data of the primary fractions
from the biologically active extract of Salvia decora revealed spectra that are characteristic for neo-clerodane-type diterpenoids. MS-guided isolation of the bioactive
fractions led to the isolation of three new chemical entities, including
two hydroxy-neo-clerodanes (1 and 2) and one acylated 5,10-seco-neo-clerodane (3), along with three known diterpenoids
(4–6), ursolic acid (7), and eupatorin (8). The structures of the new compounds
were established by analysis of the 1D and 2D NMR and MS data, whereas
their absolute configuration was deduced using a combination of experimental
and theoretical ECD data and confirmed by X-ray crystallography (1 and 4). Furthermore, compounds 1, 3, 4, and 6–8 were evaluated as hPTP1B1–400 (human protein tyrosine phosphatase) inhibitors, where 7 showed the best activity, with an IC50 value in the lower
μM range. Additionally, compound 7 was evaluated
as an α-glucosidase inhibitor. The affinity constant of the 7-hPTP1B1–400 complex was
determined by quenching fluorescence experiments (ka = 1.3 × 104 M–1),
while the stoichiometry ratio (1:1 protein–ligand) was determined
by a continuous variation method.