首页|新型γ-咔啉衍生物的合成及其抑菌活性研究

新型γ-咔啉衍生物的合成及其抑菌活性研究

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以哌啶酮和4-甲氧基苯肼为起始原料，通过Fischer吲哚合成得到中间体9，经过氧化、酰化以及烷基化构建出新型衍生物45个。所有的目标产物都进行了抗金黄色葡萄球菌、大肠埃希菌、铜绿假单胞杆菌、茄科雷尔氏菌的抑菌活性研究。结果显示:5-(4'-甲氧基苯甲酰基)-8-甲氧基-γ-咔啉(11g)、5-(2'-呋喃甲酰基)-8-甲氧基-γ-咔啉(11n)、5-(2'-溴苄基)-8-甲氧基-γ-咔啉(12f)、5-(3'-溴苄基)-8-甲氧基-γ-咔啉(12g)、5-(4'-三氟甲氧基苄基)-8-甲氧基-γ-咔啉(12h)、溴化2-(4'-氯苄基)-8-甲氧基-γ-咔啉(13e)具有良好的抑菌活性，特别是化合物12f和12h展现出了与阳性对照氨苄西林钠相当的活性，其最小抑菌浓度为8 μg/mL。探索了化合物12h对铜绿假单胞菌的作用机制，确定了其抑菌机制是通过破坏细菌的细胞壁发挥抑菌作用。进一步对该系列衍生物的构效关系进行了讨论，并总结出若干影响该类化合物生物活性的关键因素，为开发新的抗生素提供参考。
Novel γ-Carboline Derivatives as Antibacterial Agents:Synthesis and Antibacterial Evaluation
Forty-five novel 8-methoxyl-y-carboline derivatives were designed and effectively synthesized with commercially available starting materials,4-methoxyphenylhydrazine hydrochloride 7 and piperidone 8,via Fischer indole synthesis process to prepare key intermediate 9,which underwent oxidation,acylation or alkylation to yield the target derivatives.The antibacte-rial activities of all compounds were evaluated against Staphylococcus aureus(S.aureus),Escherichia coli(E.coli),Pseudo-monas aeruginosa(P.aeruginosa)and Ralstonia solanacearum(R.solanacearum).The results indicated that(8-methoxy-5H-pyrido[4,3-b]indol-5-yl)(4-methoxyphenyl)methanone(11g),furan-2-yl(8-methoxy-5H-pyrido[4,3-b]indol-5-yl)methanone(11n),5-(2-bromobenzyl)-8-methoxy-5H-pyrido[4,3-b]indole(12f),5-(3-bromobenzyl)-8-methoxy-5H-pyrido[4,3-b]indole(12g),8-methoxy-5-(4-(trifluoromethoxy)benzyl)-5H-pyrido[4,3-b]indole(12h)and 2-(4-chlorobenzyl)-8-methoxy-5H-pyri-do[4,3-b]indol-2-ium bromide(13e)showed a broad spectrum of antibacterial activity.Especially compounds 12f and 12h exhibited comparable antibacterial activity with the positive control(ampicillin sodium)with minimum inhibitory concentra-tion(MIC)value of 8 μg/mL.Moreover,membrane-active mechanism was studied further via fluorescent microscopy,which suggested that derivative 12h exerted its antibacterial effect by damaging the membranes of the bacteria.Some struc-ture-activity relationships among the forty-five derivatives are discussed and several important determinants for the activity of these compounds are identified.This work offers useful instructions for the development of new antibiotics.

8-methoxyl-N2 & N5-substituted γ-carbolinesantibacterial activitystructure-activity relationshipsmechanism

霍海波、李桂霞、王世军、韩春、师宝君、李健

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长治学院生命科学系 山西长治 046011

长治医学院基础医学部 山西长治 046011

长治学院化学系 山西长治 046011

西北农林科技大学植物保护学院 陕西杨陵 712100

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8-甲氧基-N2&N5取代γ-咔啉 抑菌活性 构效关系 抑菌机制

国家自然科学基金山西省基础研究计划山西省基础研究计划山西省基础研究计划山西省高等学校科技创新项目

822042472021030212233782021030212233822022030212121682022L510

2024

10.6023/cjoc202307018

有机化学
中国化学会,中国科学院上海有机化学研究所

有机化学

CSTPCD北大核心
影响因子：1.09
ISSN：0253-2786
年,卷(期)：2024.44(1)
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