Cytotoxic Phloroglucinols from the Leaves of <i>Myrtus communis</i>

Bioactivity-guided fractionation of a dichloromethane extract of the leaves of <i>Myrtus communis</i> led to the isolation of phloroglucinol derivatives. The structures of the new myrtucommulones J, K, and L (<b>1</b>–<b>3</b>) and the previously known myrtucommulone A (<b>4</b>) were elucidated on the basis of extensive 1D and 2D NMR experiments as well as high-resolution mass spectrometry. Myrtucommulone J was obtained as a tautomeric pair (<b>1</b>/<b>1a</b>). The compounds were tested in vitro for their cytotoxic and antibacterial activities

Methoxyflavones from <i>Stachys glutinosa</i> with Binding Affinity to Opioid Receptors: In Silico, in Vitro, and in Vivo Studies

Fractionation of the bioactive dichloromethane extract from the aerial parts of <i>Stachys glutinosa</i> led to the isolation of four flavones, xanthomicrol (<b>1</b>), sideritoflavone (<b>2</b>), 8-methoxycirsilineol (<b>3</b>), and eupatilin (<b>4</b>), along with two <i>neo</i>-clerodane diterpenes, roseostachenone (<b>8</b>) and a new compound, 3α,4α-epoxyroseostachenol (<b>7</b>). In order to study structure–activity relationships, two methoxyflavones [5-demethyltangeretin (<b>5</b>) and tangeretin (<b>6</b>)] were synthesized by the methoxylation of xanthomicrol. The isolated compounds (<b>1</b>–<b>4</b>, <b>7</b>, and <b>8</b>) as well as the xanthomicrol semisynthetic derivatives (<b>5</b> and <b>6</b>) were evaluated for their binding affinity to the μ and δ opioid receptors. Xanthomicrol was the most potent binder to both μ and δ receptors, with a <i>K</i>_i value of 0.83 and 3.6 μM, respectively. Xanthomicrol administered intraperitoneally in mice at a dose of 80 mg/kg significantly reduced morphine-induced antinociception in the tail flick test. Our results suggested that xanthomicrol is a μ opioid receptor antagonist. Docking experiments were carried out to acquire a deeper understanding about important structural aspects of binding of xanthomicrol. In summary, these data suggest that xanthomicrol is a valuable structure for further development into a potential μ opioid receptor antagonist

Phenylpropenoids from <i>Bupleurum fruticosum</i> as Anti-Human Rhinovirus Species A Selective Capsid Binders

The dichloromethane extract of the leaves of <i>Bupleurum fruticosum</i> was found to inhibit the replication of human rhinovirus (HRV) serotypes 14 and 39. Bioassay-guided fractionation led to the isolation of seven phenylpropenol derivatives (<b>3</b>–<b>9</b>), two polyacetylenes (<b>1</b> and <b>2</b>), and one monoterpene (<b>10</b>). Compounds <b>1</b> and <b>10</b> were identified as previously undescribed secondary metabolites after extensive 1D and 2D NMR experiments as well as high-resolution mass spectrometry. Compounds <b>2</b>, <b>4</b>, and <b>5</b> showed a selective inhibition of viral replication against HRV39 serotype, with <b>2</b> and <b>4</b> being the most active, with EC₅₀ values of 1.8 ± 0.02 and 2.4 ± 0.04 μM. Mechanism of action studies indicated that <b>4</b> behaves not only as a capsid binder, interfering with the early phases of virus replication, but also as a late-phase replication inhibitor. Docking experiments were performed to confirm the ability of the antiviral phenylpropenoids to selectively fit into the hydrophobic pocket of VP1-HRV39