Chaetoglobosins from Chaetomium globosum, an Endophytic Fungus in Ginkgo biloba, and Their Phytotoxic and Cytotoxic Activities

In preceding studies, cultivation of Chaetomium globosum, an endophytic fungus in Ginkgo biloba, produced five cytochalasan mycotoxins, chaetoglobosins A, G, V, V_b, and C (<b>1</b>–<b>5</b>), in three media. In the present work, five known chaetoglobosins, C, E, F, F_ex, and 20-dihydrochaetoglobosin A (<b>5</b>–<b>9</b>), together with the four known compounds (<b>11</b>–<b>14</b>), were isolated from the MeOH extracts of the solid culture of the same endophyte. The structures of these metabolites were elucidated on the basis of spectroscopic analysis. Treatment of chaetoglobosin F (<b>7</b>) with (diethylamino)­sulfur trifluoride (DAST) in dichloromethane afforded an unexpected fluorinated chaetoglobosin, named chaetoglobosin F_a (<b>10</b>), containing an oxolane ring between C-20 and C-23. The phytotoxic effects of compounds <b>1</b>, <b>3</b>–<b>8</b>, and <b>10</b> were assayed on radish seedlings; some of these compounds (<b>1</b>, <b>3</b>, and <b>6</b>–<b>8</b>) significantly inhibited the growth of radish (Raphanus sativus) seedlings with inhibitory rates of >60% at a concentration of 50 ppm, which was comparable or superior to the positive control, glyphosate. In addition, the cytotoxic activities against HCT116 human colon cancer cells were also tested, and compounds <b>1</b> and <b>8</b>–<b>10</b> showed remarkable cytotoxicity with IC₅₀ values ranging from 3.15 to 8.44 μM, in comparison to the positive drug etoposide (IC₅₀ = 2.13 μM). The epoxide ring between C-6 and C-7 or the double bond at C-6(12) led to a drastically increased cytotoxicity, and chaetoglobosin F_a (<b>10</b>) displayed a markedly increased cytotoxicity but decreased phytotoxicity