Antiviral Activity of Flexibilane and Tigliane Diterpenoids from <i>Stillingia lineata</i>

In an effort to identify new potent and selective inhibitors of chikungunya virus and HIV-1 and HIV-2 virus replication, the endemic Mascarene species <i>Stillingia lineata</i> was investigated. LC/MS and bioassay-guided purification of the EtOAc leaf extract using a chikungunya virus-cell-based assay led to the isolation of six new (<b>4</b>–<b>9</b>) and three known (<b>1</b>–<b>3</b>) tonantzitlolones possessing the rare C₂₀-flexibilane skeleton, along with tonantzitloic acid (<b>10</b>), a new linear diterpenoid, and three new (<b>11</b>, <b>13</b>, and <b>15</b>) and two known (<b>12</b> and <b>14</b>) tigliane-type diterpenoids. The planar structures of the new compounds and their relative configurations were determined by spectroscopic analysis, and their absolute configurations were determined through comparison with literature data and from biogenetic considerations. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, and, for compounds <b>11</b>–<b>15</b>, the HIV-1 and HIV-2 viruses. Compounds <b>12</b>–<b>15</b> were found to be the most potent and are selective inhibitors of CHIKV, HIV-1, and HIV-2 replication. In particular, compound <b>14</b> inhibited CHIKV replication with an EC₅₀ value of 1.2 μM on CHIKV and a selectivity index of >240, while compound <b>15</b> inhibited HIV-1 and HIV-2 with EC₅₀ values of 0.043 and 0.018 μM, respectively. It was demonstrated further that potency and selectivity are sensitive to the substitution pattern on the tigliane skeleton. The cytotoxic activities of compounds <b>1</b>–<b>10</b> were evaluated against the HCT-116, MCF-7, and PC3 cancer cell lines

カラバルガスン ヒブン カンブン バン ノ シンコウテイ ト ヤクチュウ

An ethyl acetate extract of <i>Psiadia arguta</i> leaves showed in vitro antiplasmodial activity against <i>Plasmodium falciparum</i> with IC₅₀ values of 12.3 ± 2.4 μg/mL (3D7 strain) and 13.5 ± 3.4 μg/mL (W2 strain). Phytochemical investigation led to the isolation and characterization of 16 compounds including four new diterpenoids: labdan-8α-ol-15-yl-(formate) (<b>1</b>), labdan-8α-ol-15-yl-(2-methylbutanoate) (<b>2</b>), labdan-8α-ol-15-yl-(3-methylpentanoate) (<b>3</b>), and labdan-8α-ol-15-yl-(labdanolate) (<b>4</b>). The latter compounds were characterized by spectroscopic methods (1D and 2D NMR, HRMS, and IR). The in vitro antiplasmodial activities of all compounds were evaluated. The known compounds labdan-13­(<i>E</i>)-en-8α-ol-15-yl acetate (<b>5</b>), labdan-8α-ol-15-yl acetate (<b>6</b>), 13-<i>epi</i>-sclareol (<b>7</b>), labdan-13­(<i>E</i>)-ene-8α,15-diol (<b>8</b>), and (8<i>R</i>,13<i>S</i>)-labdane-8α,15-diol (<b>9</b>) exhibited antiplasmodial effects, with IC₅₀ values of 29.1, 33.2, 35.0, 36.6, and 22.2 μM, respectively