Antibacterial Labdane Diterpenoids from Vitex vestita

A large-scale in vitro screening
of tropical plants using an antibacterial
assay permitted the selection of several species with significant
antibacterial activities. Bioassay-guided purification of the dichloromethane
extract of the leaves of the Malaysian species Vitex
vestita, led to the isolation of six new labdane-type
diterpenoids, namely, 12-epivitexolide A (2), vitexolides
B and C (3 and 4), vitexolide E (8), and vitexolins A and B (5 and 6), along
with six known compounds, vitexolides A (1) and D (7), acuminolide (9), 3β-hydroxyanticopalic
acid (10), 8α-hydroxyanticopalic acid (11), and 6α-hydroxyanticopalic acid (12). Their
structures were elucidated on the basis of 1D and 2D NMR analyses
and HRMS experiments. Both variable-temperature NMR spectroscopic
studies and chemical modifications were performed to investigate the
dynamic epimerization of the γ-hydroxybutenolide moiety of compounds 1–4. Compounds were assayed against a
panel of 46 Gram-positive strains. Vitexolide A (1) exhibited
the most potent antibacterial activity with minimal inhibitory concentration
values ranging from 6 to 96 μM, whereas compounds 2 and 6–9 showed moderate antibacterial
activity. The presence of a β-hydroxyalkyl-γ-hydroxybutenolide
subunit contributed significantly to antibacterial activity. Compounds 1–4 and 6–9 showed cytotoxic activities against the HCT-116 cancer cell line
(1 < IC50s < 10 μM) and human
fetal lung fibroblast MRC5 cell line (1 < IC50s < 10 μM for compounds 1, 2, 7, 8, and 9).