Design, Semisynthesis, Insecticidal and Antibacterial Activities of a Series of Marine-Derived Geodin Derivatives and Their Preliminary Structure–Activity Relationships

Abstract

To enhance the biological activity of the natural product geodin (<b>1</b>), isolated from the marine-derived fungus <i>Aspergillus</i> sp., a series of new ether derivatives (<b>2</b>-<b>37</b>) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against <i>Helicoverpa armigera</i> Hübner than <b>1</b>. In particular, <b>15</b> showed potent insecticidal activity with an IC₅₀ value of 89 μM, comparable to the positive control azadirachtin (IC₅₀ = 70 μM). Additionally, <b>5</b>, <b>12</b>, <b>13</b>, <b>16</b>, <b>30</b> and <b>33</b> showed strong antibacterial activity against <i>Staphylococcus aureus</i> and <i>Aeromonas salmonicida</i> with MIC values in the range of 1.15-4.93 μM. The preliminary structure-activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into <b>1</b> and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.