title: Antibacterial Labdane Diterpenoids from Vitex vestita.
abstract: 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).
authors.affiliation: †Centre de Recherche de Gif, LabEx CEBA, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, 91198 Gif-sur-Yvette, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Corlay
authors.forename: Marylin
authors.initials: M
authors.lastname: Lecsö-Bornet
authors.affiliation: †Centre de Recherche de Gif, LabEx CEBA, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, 91198 Gif-sur-Yvette, France.
authors.forename: Erell
authors.initials: E
authors.lastname: Leborgne
authors.affiliation: †Centre de Recherche de Gif, LabEx CEBA, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, 91198 Gif-sur-Yvette, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: †Centre de Recherche de Gif, LabEx CEBA, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, 91198 Gif-sur-Yvette, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cachet
authors.affiliation: †Centre de Recherche de Gif, LabEx CEBA, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, 91198 Gif-sur-Yvette, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bignon
authors.affiliation: †Centre de Recherche de Gif, LabEx CEBA, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, 91198 Gif-sur-Yvette, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Roussi
authors.forename: Marie-Jose
authors.initials: MJ
authors.lastname: Butel
authors.affiliation: ∥Department of Chemistry, University Malaya, 59100 Kuala Lumpur, Malaysia.
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.affiliation: †Centre de Recherche de Gif, LabEx CEBA, Institut de Chimie des Substances Naturelles (ICSN), CNRS UPR 2301, 91198 Gif-sur-Yvette, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D008296:Malaysia; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D020950:Vitex / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C433017:labdane; C000601096:vitexolide A