CN113350327A - 肉桂酸及其衍生物作为抗菌剂在抑制人源性病菌中的应用 - Google Patents
肉桂酸及其衍生物作为抗菌剂在抑制人源性病菌中的应用 Download PDFInfo
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Abstract
本发明公开了一种肉桂酸及其系列衍生物的新用途,即作为抗菌剂在抗人源性病菌中的应用,属于天然药物化学领域。本发明通过27种肉桂酸及其系列衍生物对人源性病菌的抗菌活性进行研究表明,以天然产物肉桂酸为化学骨架衍生的一系列化合物作为杀菌剂,对于与人源性病菌大肠杆菌、金黄色葡萄球菌具有良好的抗菌活性,部分化合物浓度在0.1 mg/mL时,抑制率仍在90%以上,可作为新的杀菌先导化合物进行生物合理性设计与开发。另外。肉桂酸及其系列衍生物具有低毒、低残留、环境相容、不易产生耐药性等特点和优势,具有开发成为绿色、无污染、无公害新型杀菌剂的潜力。
Description
技术领域
本发明涉及一种肉桂酸及其衍生物的新用途,即作为抗菌剂在抑制人源性病菌中的应用,属于天然药物化学领域。
背景技术
人源性病菌主要包括大肠杆菌Escherichia coli ATCC 25922、金黄色葡萄球菌Staphyloccocus aureus subsp. Newman和白色念珠菌Canidia albicans ATCC 24433三种。其中,大肠杆菌是临床感染中最常见的革兰阴性菌之一,主要通过粪-口传播途径传播,在一定条件下可引起人和多种动物发生胃肠道、尿道等多种局部组织器官感染。金黄色葡萄球菌是临床感染中最常见的革兰阳性菌之一,常见于皮肤表面及上呼吸道黏膜,在一定条件下能够产生肠毒素,引起食物中毒,是引起食物中毒的常见致病菌。
多药耐药细菌病原体的日益出现和传播加速了对新抗生素的需求。天然产物主导着发现抗菌剂的首选化学骨架。肉桂酸是植物组织中苯丙氨酸脱去氨基后的代谢产物,广泛分布于蜂胶、蔬菜和水果等天然物质中,由于其结构简单、原料易得、毒性低且具有广泛的生物活性,已成为抗菌领域重要研究方向之一。
发明内容
本发明的目的是对肉桂酸及其系列衍生物对人源性病菌的抑制作用进行研究,以期用于制备治疗大肠杆菌Escherichia coli ATCC 25922、金黄色葡萄球菌Staphyloccocus aureus sp. Newman引起的人畜共患疾病。
为了研究肉桂酸及其衍生物对大肠杆菌Escherichia coli ATCC 25922和金黄色葡萄球菌Staphyloccocus aureus sp. Newman的抗菌活性,本发明测定了27种化合物浓度为0.8 mg/mL时对大肠杆菌和金黄色葡萄球菌的抑制率。对于抑制率大于90%的化合物,通过二倍稀释法进行低浓度活性测定。
、肉桂酸衍生物对人源细菌的活性测定
本实验中所用的细菌为实验室-80℃含30%甘油冻存的菌种。将冻存细菌取出,在人源细菌的NB固体培养基(牛肉膏:3 g,蛋白胨:10g,氯化钠:5g,琼脂:15 g,蒸馏水:1 L,pH7.0;121℃灭菌20 min)上面进行划线,在37℃下恒温培养直到长出单菌落。分别挑取NB固体培养基上单菌落至人源细菌NB液体培养基(牛肉膏:3 g,蛋白胨:10g,氯化钠:5g,蒸馏水:1 L,pH7.0;121℃灭菌20 min)中,在37℃、180 rpm恒温摇床振荡培养到对数生长期。将处于对数生长期的细菌用NB液体培养基稀释至约106 CFU/mL备用。将化合物分别用DMSO溶解,加入NB液体培养基中,混合均匀,配制成浓度为1.6 mg/mL的含药NB液体培养基。取50 μL含药培养基和相同体积的含约106 CFU/mL细菌培养物加入到96孔板的孔中,最终给药浓度为0.8 mg/mL。含等量DMSO的相同浓度100 μL菌液做对照。将96孔板在37℃恒温培养箱中培养24-48 h直至对照组菌液长出,在酶标仪上测定孔中菌液的OD值(OD600)。并且另外测定100 μL NB液体培养基和浓度为0.8 mg/mL药剂的OD值,对培养基和药剂本身造成的OD值进行矫正。校正OD值和抑制率的计算公式如下:
校正OD值 = 含菌培养基OD值-无菌培养物OD值;
抑制率 =(校正后对照培养基菌液OD值-校正后含药培养基OD值)/校正后对照培养基菌液OD值 × 100%
所有实验设置三个重复,测定得到化合物的抑制率见表1。
由表1的测结果可知,本发明涉及的肉桂酸及其衍生物对大肠杆菌、金黄色葡萄球菌均具有很好的抑制作用,且对金黄色葡萄球菌的抑制作用更为突出。
、高活性肉桂酸及其衍生物低浓度下对人源细菌的活性测定
将化合物的含药NB培养基在96孔板中通过二倍稀释法稀释得到系列浓度的50 μL含药培养基,然后根据上述相同的试验方法测定系列浓度对应的抑制率。测定得到的活性数据见表2。
由表2的测结果可知,肉桂酸(1)在低浓度时也表现出良好的抗菌活性,其衍生物如10(4-Cl)、13(4-Br)均提高了对植物病原细菌和金黄色葡萄球菌的活性,衍生物如11(2,4-Cl)、12(3,4-Cl)、13(4-Br)、15(2-CF3)、16(4-CF3)、17(3,5-CF3)、27(3-OCF3)明显提高了抗金黄色葡萄球菌的活性。
上述研究表明,肉桂酸及其系列衍生物对大肠杆菌Escherichia coli ATCC25922,金黄色葡萄球菌Staphyloccocus aureus sp. Newman等人源性细菌均具有一定的抑制作用。部分化合物浓度在0.1 mg/mL时,抑制率仍在90%以上,可作为新的杀菌先导化合物进行生物合理性设计与开发。另外。肉桂酸及其系列衍生物具有低毒、低残留、环境相容、不易产生耐药性等特点和优势,具有开发成为绿色、无污染、无公害新型杀菌剂的潜力。
表1、2中,肉桂酸及其衍生物化合物1-27的化学结构式如下:
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CN112830923A (zh) * | 2019-11-25 | 2021-05-25 | 北京中医药大学 | 具有选择性抗菌作用的系列苯丙烯酸-异喹啉生物碱络合物及其无载体纳米药物的制备 |
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