CN114097807B - 巴多索隆类化合物在抗农业病原真菌中的用途 - Google Patents
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Abstract
本发明属于药物化学领域,公开了巴多索隆类化合物巴多索隆和甲基巴多索隆防治由农业病原真菌核盘菌Sclerotinia sclerotiorum、立枯丝核菌Rhizoctonia solani、禾谷镰刀菌Fusarium graminearum、灰葡萄孢Botrytis cinerea、稻瘟病菌Magnaporthe oryzae以及辣椒疫霉Phytophthora capsici引起的农业病害。巴多索隆对所测试的大部分病原菌具有较高的活性;甲基巴多索隆对立枯丝核菌和灰葡萄孢活性显著,两者具有进一步研究与开发成新型农用杀菌剂的价值。
Description
技术领域
本发明属于药物化学领域,公开了巴多索隆类化合物巴多索隆和甲基巴多索隆在抗农业病原真菌核盘菌Sclerotinia sclerotiorum、立枯丝核菌Rhizoctonia solani、禾谷镰刀菌Fusarium graminearum、灰葡萄孢Botrytis cinerea、稻瘟病菌Magnaportheoryzae以及辣椒疫霉Phytophthora capsici引起的植物性病害的新用途。
背景技术
植物病害是影响农业生产的主要因素之一,迄今,植物病害主要还是采用化学药剂防治,但由于化学药剂长期使用后,会给人类带来一系列严重的问题:残留、污染、有害生物抗药性产生、伤害非靶标生物,以至于破坏生态平衡。因此,研究植物病害无公害防治措施势在必行,并已成为研究的热点、世人关注的焦点,但在目前我国只有少量的生防菌及代谢产物应用于生物防治,且生防产品大多是活菌制剂,易受环境因素的影响,在田间的防治效果很不稳定。所以利用新策略,发现新抗菌化合物,将已有的化合物发挥至最大化是值得关注和研究的问题。
巴多索隆和甲基巴多索隆是齐墩果酸衍生的半合成三萜类化合物,可以激活Nrf2并抑制NF-κB通路,减少促炎信号。目前,甲基巴多索隆已被开发为口服抗氧化和炎症调节剂。据最新报道,新冠肺炎患者的肺组织中的Nrf2途径受到抑制,病毒感染干扰了Nrf2下游基因的表达。因此,Nrf2激活剂巴多索隆和甲基巴多索隆可通过多种机制发挥抗病毒作用,包括抑制病毒复制、促进炎症消退、提供稳健的细胞保护和促进组织修复等,具有良好的临床应用价值。
本课题组利用老药新用策略对大量商业化医用药物筛选中发现,巴多索隆和甲基巴多索隆对农业病原真菌表现出优异的抑制作用。目前巴多索隆和甲基巴多索隆还没有关于抗农业病原菌的活性报道,可以用于新型农用抗菌剂的创新,具有实现老药新用的潜力,可进一步进行研究开发。
发明内容
本发明的目的是针对防治农业病害中产生的问题,提供巴多索隆和甲基巴多索隆在抗农业病原真菌中的新用途。
巴多索隆和甲基巴多索隆可防治由核盘菌、立枯丝核菌、禾谷镰刀菌、灰葡萄孢、稻瘟病菌以及辣椒疫霉引起的植物性病害。
本发明的优势主要有巴多索隆和甲基巴多索隆对农业病原真菌表现出优异的抗菌活性,且毒性低,具有进一步开发为新型农用抗菌剂的潜力。
具体实施方式
为了更好地理解本发明,通过以下具体实施例对本发明的上述内容做进一步的详细说明。但不应将此理解为对本发明的限制。下列实施例中所述实验方法,如无特殊说明,均为常规方法。
实施例1:巴多索隆和甲基巴多索隆通过商业化购置,其CAS号和纯度为:(1)巴多索隆、CAS:218600-44-3、纯度:98%;(2)甲基巴多索隆、CAS:218600-53-4、纯度:≥98%。
实施例2 巴多索隆和甲基巴多索隆结构式见化学式I:
实施例3:巴多索隆和甲基巴多索隆对农业病原真菌活性测定
本实验中所用的农业病原菌为实验室4℃保存的菌种,采用的培养基为马铃薯琼脂葡萄糖培养基(简称PDA)。PDA培养基配方:马铃薯(去皮)200g,葡萄糖20g,琼脂15g,蒸馏水1000mL,自然PH。
PDA培养基配置方法:将马铃薯洗净去皮,称200g切成小块,蒸馏水煮20min左右(土豆块软而不烂),用八层纱布过滤,用蒸馏水将滤液补足至1000mL,加入15g琼脂,20g葡萄糖,搅拌使其充分溶解后,分装于三角瓶中,121℃灭菌20分钟,冷却后备用。室内活性测定采用菌丝生长速率法。
菌种活化:将农业病原菌在PDA平板上25℃培养3~6天。
制备药板:将PDA培养基加热熔化,冷却至45-50℃,分别加入不同浓度混配物制成带药平板。
接种培养:在超净台中,用打孔器在培养3~6天的菌丝边缘(生长状况尽量一致)打取菌饼(直径5mm),再用接种针挑至药板中央,然后在培养箱(25℃)中倒置培养。
结果测定:空白对照组菌丝长满后,采用十字交叉法测得给药组菌丝的生长直径,计算抑制率。
抑制率(%)=(对照菌丝直径-处理菌丝直径)/(对照菌丝直径-菌饼直径)×100,每个浓度设置3次平行实验,测定得到化合物的抑制率见表1。
表1 巴多索隆和甲基巴多索隆对抗农业病原真菌的抑制作用
上述结果表明:巴多索隆和甲基巴多索隆对部分病原菌抑菌效果表现优异,选择高活性化合物做毒力作用测定。将高活性化合物用0.5%的DMSO溶解后,加入无菌的PDA培养基制成不同浓度的带药培养基,对病原菌抑菌率降低到50%以下,选取嘧菌酯作为阳性对照。利用SPSS 26.0求出毒力回归方程(y=a+bx)和相关系数(r),并计算出对供试植物病原真菌的EC50,测定得到的活性数据见表2。
表2.巴多索隆和甲基巴多索隆抗农业病原真菌的EC50值
由表1、2生测结果可知,本发明涉及的巴多索隆和甲基巴多索隆对所测试病原菌具有一定的抗菌活性。其中浓度100μg/mL时,巴多索隆对所测试病原菌抑菌率为68.16%~80.03%,对立枯丝核菌、核盘菌、稻瘟病菌和辣椒疫霉的EC50为4.04μg/mL~5.30μg/mL,均高于对照药剂嘧菌酯;浓度100μg/mL时,甲基巴多索隆对立枯丝核菌和灰葡萄孢具有较高的抗菌性,其抑菌率分别为75.15%和88.74%,EC50分别为0.56μg/mL和1.72μg/mL,均高于对照药剂嘧菌酯。综上所述,本发明所述的巴多索隆和甲基巴多索隆在农业上具有进一步研究和开发的价值。
Claims (7)
1.巴多索隆和甲基巴多索隆在抗6种农业病原真菌中的用途,所述6种农业病原真菌是立枯丝核菌,核盘菌,禾谷镰刀菌,灰葡萄孢,稻瘟病菌和辣椒疫霉。
2.巴多索隆和甲基巴多索隆在防治立枯丝核菌引起的植物病害中的用途。
3.巴多索隆和甲基巴多索隆在防治核盘菌引起的植物病害中的用途。
4.巴多索隆和甲基巴多索隆在防治禾谷镰刀菌引起的植物病害中的用途。
5.巴多索隆和甲基巴多索隆在防治灰葡萄孢引起的植物病害中的用途。
6.巴多索隆和甲基巴多索隆在防治稻瘟病菌引起的植物病害中的用途。
7.巴多索隆和甲基巴多索隆在防治辣椒疫霉引起的植物病害中的用途。
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