何丹婵, 姜熙, 杨青. 亚洲玉米螟几丁质酶的双靶向天然产物抑制剂及其抑制机理[J]. 农药学学报, 2022, 24(5): 1171-1178. DOI: 10.16801/j.issn.1008-7303.2022.0044
    引用本文: 何丹婵, 姜熙, 杨青. 亚洲玉米螟几丁质酶的双靶向天然产物抑制剂及其抑制机理[J]. 农药学学报, 2022, 24(5): 1171-1178. DOI: 10.16801/j.issn.1008-7303.2022.0044
    HE Danchan, JIANG Xi, YANG Qing. Dual-targeted natural product inhibitors of Ostrinia furnacalis chitinases and inhibitory mechanisms[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1171-1178. DOI: 10.16801/j.issn.1008-7303.2022.0044
    Citation: HE Danchan, JIANG Xi, YANG Qing. Dual-targeted natural product inhibitors of Ostrinia furnacalis chitinases and inhibitory mechanisms[J]. Chinese Journal of Pesticide Science, 2022, 24(5): 1171-1178. DOI: 10.16801/j.issn.1008-7303.2022.0044

    亚洲玉米螟几丁质酶的双靶向天然产物抑制剂及其抑制机理

    Dual-targeted natural product inhibitors of Ostrinia furnacalis chitinases and inhibitory mechanisms

    • 摘要: 多个几丁质酶可协同催化昆虫表皮几丁质的水解,在昆虫蜕皮发育过程中发挥不可或缺的作用,是潜在的绿色杀虫剂作用分子靶标。本文通过对1680种天然产物进行高通量筛选,获得了3个靶向亚洲玉米螟Ostrinia furnacalis来源的几丁质酶OfChtI和OfChi-h的双靶标抑制剂:漆树酸、邻苯二甲酸二 (2-乙基己基) 酯 (DEHP) 和紫菀酮。它们对OfChtI的抑制常数 (Ki) 分别为0.57、0.53 和3.95 μmol/L;对OfChi-h的抑制常数分别为0.48、1.42 和27.33 μmol/L。分子对接结果表明,三者均通过疏水堆积作用结合在靶标酶的底物结合位点上。此外,漆树酸的1位羧基氧原子作为氢键受体,与OfChtI的Arg274和OfChi-h的Arg439侧链胍基氢原子形成氢键。DEHP的羰基和烷氧基氧原子作为氢键受体,与OfChtI的Arg274侧链胍基氢原子形成氢键;DEHP的烷氧基氧原子作为氢键受体,与OfChi-h的Arg439侧链胍基氢原子形成氢键。杀虫活性测定结果表明,在2 mmol/L浓度下,漆树酸和DEHP对亚洲玉米螟幼虫的致死率为33.3%,紫菀酮没有表现出明显的杀虫活性。该研究对于同时靶向多个几丁质酶的新型绿色农药的创制具有参考意义。

       

      Abstract: Multiple chitinases are required for effective hydrolysis of insect epidermal chitin and play an indispensable role in insect molting. As chitin is absent in plants and mammals, these enzymes can be potential targets for the design of green insecticides. In this paper, three dual-target inhibitors against the Asian corn borer (Ostrinia furnacalis)-derived chitinases OfChtI and OfChi-h, anacardic acid, di(2-ethylhexyl) phthalate (DEHP), and shionone, were obtained through high-throughput screening of 1680 natural products. The respective Ki values for OfChtI are 0.57, 0.53 and 3.95 μmol/L, and are 0.48, 1.42 and 27.33 μmol/L for OfChi-h. The molecular docking results showed that all three inhibitors were bound to the substrate-binding sites of the target enzymes through hydrophobic stacking interaction. In addition, the 1-carboxyl oxygen atom of anacardic acid, as a hydrogen bond acceptor, formed hydrogen bonds with guanidine hydrogen atoms of Arg274 side chain in OfChtI and Arg439 side chain in OfChi-h, respectively. The carbonyl and etheryl oxygen atoms of DEHP, as hydrogen bond receptors, formed hydrogen bonds with hydrogen atoms of Arg274 guanidine group side chain in OfChtI; the etheryl oxygen atom of DEHP, as a hydrogen bond acceptor, formed hydrogen bond with guanidine hydrogen atom of Arg439 side chain in OfChi-h. The insecticidal activity was determined to be 33.3% for anacardic acid and DEHP at 2 mmol/L, while shionone showed no obvious insecticidal activity. This study may provide a clue for the development of novel green pesticides targeting multiple chitinases simultaneously.

       

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