Synthesis, Antifungal Activity, 3D-QSAR, and Molecular Docking Study of Novel Menthol-Derived 1,2,4-Triazole-thioether Compounds
A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 μg/mL, some of the target compo...
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| Autores principales: | , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/9b3f87e26e7a459a8631390e1c4c3cdb |
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| Sumario: | A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 μg/mL, some of the target compounds exhibited good inhibitory activity against the tested fungi, especially against <i>Physalospora piricola</i>. Compounds <b>5b</b> (R = <i>o</i>-CH<sub>3</sub> Ph), <b>5i</b> (R = <i>o</i>-Cl Ph), <b>5v</b> (R = <i>m</i>,<i>p</i>-OCH<sub>3</sub> Ph) and <b>5x</b> (R = <i>α</i>-furyl) had inhibition rates of 93.3%, 79.4%, and 79.4%, respectively, against <i>P. piricola</i>, much better than that of the positive control chlorothalonil. Compounds <b>5v</b> (R = <i>m</i>,<i>p</i>-OCH<sub>3</sub> Ph) and <b>5g</b> (R = <i>o</i>-Cl Ph) held inhibition rates of 82.4% and 86.5% against <i>Cercospora arachidicola</i> and <i>Gibberella zeae</i>, respectively, much better than that of the commercial fungicide chlorothalonil. Compound <b>5b</b> (R = <i>o</i>-CH<sub>3</sub> Ph) displayed antifungal activity of 90.5% and 83.8%, respectively, against <i>Colleterichum orbicalare</i> and <i>Fusarium oxysporum</i> f. sp. <i>cucumerinum</i>. Compounds <b>5m</b> (R = <i>o</i>-I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, against <i>F. oxysporum</i> f. sp. <i>cucumerinu</i>, <i>Bipolaris maydis</i> and <i>C. orbiculare</i>. Furthermore, compound <b>5b</b> (R = <i>o</i>-CH<sub>3</sub> Ph) showed the best and broad-spectrum antifungal activity against all the tested fungi. To design more effective antifungal compounds against <i>P. piricola</i>, 3D-QSAR analysis was performed using the CoMFA method, and a reasonable 3D-QSAR model (<i>r</i><sup>2</sup> = 0.991, <i>q</i><sup>2</sup> = 0.514) was established. The simulative binding pattern of the target compounds with cytochrome P450 14α-sterol demethylase (CYP51) was investigated by molecular docking. |
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