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 (<b>2</b>), vitexolides B and C (<b>3</b> and <b>4</b>), vitexolide E (<b>8</b>), and vitexolins A and B (<b>5</b> and <b>6</b>), along with six known compounds, vitexolides A (<b>1</b>) and D (<b>7</b>), acuminolide (<b>9</b>), 3β-hydroxyanticopalic acid (<b>10</b>), 8α-hydroxyanticopalic acid (<b>11</b>), and 6α-hydroxyanticopalic acid (<b>12</b>). 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 <b>1</b>–<b>4</b>. Compounds were assayed against a panel of 46 Gram-positive strains. Vitexolide A (<b>1</b>) exhibited the most potent antibacterial activity with minimal inhibitory concentration values ranging from 6 to 96 μM, whereas compounds <b>2</b> and <b>6</b>–<b>9</b> showed moderate antibacterial activity. The presence of a β-hydroxyalkyl-γ-hydroxybutenolide subunit contributed significantly to antibacterial activity. Compounds <b>1</b>–<b>4</b> and <b>6</b>–<b>9</b> showed cytotoxic activities against the HCT-116 cancer cell line (1 < IC₅₀<i>s</i> < 10 μM) and human fetal lung fibroblast MRC5 cell line (1 < IC₅₀<i>s</i> < 10 μM for compounds <b>1</b>,<b> 2</b>,<b> 7</b>,<b> 8</b>, and <b>9</b>)