Discovery of Indoloazepinone Analogues as Novel Antiviral, Antiphytopathogenic Fungus, and Insecticidal Agents
Discovery of Indoloazepinone Analogues as Novel Antiviral, Antiphytopathogenic Fungus, and Insecticidal Agents
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DOI：
10.1021/acsagscitech.2c00059
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发表时间：
2022-06
期刊：
影响因子：
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通讯作者：
Yanke Hao;Hongfu He;Pan Zhou;Kaikai Niu;Hongjian Song;Yuxiu Liu;Jingjing Zhang;D. Hu;Qingmin Wang;Baoan Song
中科院分区：
文献类型：
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作者：
Yanke Hao;Hongfu He;Pan Zhou;Kaikai Niu;Hongjian Song;Yuxiu Liu;Jingjing Zhang;D. Hu;Qingmin Wang;Baoan Song
阿尔地辛生物碱具有广泛的生物活性，也是多种天然产物的核心骨架，但其溶解性差影响了其药效。为了提高吲哚并氮杂卓酮的溶解性和生物活性，设计合成了一系列含肟醚、肟酯、腙和酯基的吲哚并氮杂卓酮衍生物，并对其抗病毒、杀菌和杀幼虫活性进行了评价。这些吲哚并氮杂卓酮衍生物的溶解性比阿地辛有所提高，且大多数化合物对辣椒温和斑驳病毒（PMMoV）表现出良好的抗病毒活性，其中4-氯苯甲酰基肟酯衍生物5i在体内表现出最高的保护、治疗和灭活活性（500 mg/L时抑制率分别为61 ± 4.1、60 ± 5.3和74 ± 4.2%），与宁南霉素（500 mg/L时抑制率分别为59 ± 2.2、58 ± 0.7和81 ± 4.8%）相当。化合物5i（大鼠急性口服毒性试验，LD 50> 2000 mg/kg）成为抗PMMoV药物的有希望的候选物。大部分化合物具有广谱杀菌活性，其中化合物5a和5 f对辣椒疫霉菌具有选择性杀菌活性。此外，这些化合物对小菜蛾和淡色库蚊也表现出较好的杀虫活性。
Aldisine alkaloid has a wide range of biological activities and is also the core skeleton of a variety of natural products, but its poor solubility affects its efficacy. In order to improve its solubility and biological activity, a series of indoloazepinone derivatives containing oxime ether, oxime ester, hydrazone, and ester moieties were designed and synthesized, and their antiviral, fungicidal, and larvicidal activities were evaluated. The solubility of these indoloazepinone derivatives improved in comparison with that of aldisine, and most of these compounds showed good antiviral activities against pepper mild mottle virus (PMMoV), among which the 4-chlorobenzoyl oxime ester derivative5ishowed the highest protection, curative, and inactivation activities in vivo (inhibition rate 61 ± 4.1, 60 ± 5.3, and 74 ± 4.2% at 500 mg/L, respectively), which was comparable to that of ningnanmycin (59 ± 2.2, 58 ± 0.7, and 81 ± 4.8% at 500 mg/L, respectively). Compound5i(the rat acute oral toxicity test, LD50> 2000 mg/kg) emerged as a promising candidate for anti-PMMoV drug. Most of these compounds have broad-spectrum fungicidal activities, and5aand5fshowed selectively fungicidal activities againstPhytophthora capsici. In addition, these compounds also showed good larvicidal activities againstPlutella xylostellaandCulex pipiens pallens.