Natural product bufotenine(5)which could be isolated from Venenum Bufonis,has been widely used as a tool in central nervous system(CNS)studies.We present here its quaternary ammonium salt(6)which was synthesized with ...Natural product bufotenine(5)which could be isolated from Venenum Bufonis,has been widely used as a tool in central nervous system(CNS)studies.We present here its quaternary ammonium salt(6)which was synthesized with high yields using 5-benzyloxyindole as raw materials,and we firstly discover its analgesic effects in vivo.The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice.Moreover,the combination of compound 6 and morphine has a synergistic effect.We intended to explain the molecular mechanism of this effect.Therefore,36 analgesic-related targets(including 15 G protein-coupled receptors,6 enzymes,13 ion channels,and 2 others)were systemically evaluated using reverse docking.The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase(AChE)orα_(4)β_(2) nicotinic acetylcholine receptor(nAChR).This study provides practitioners a new insight of analgesic effects.展开更多
文摘目的以洋金花Datura metel和木本曼陀罗Brugmansia arborea为材料,分析其叶绿体基因组结构和特征,基于叶绿体组数据探讨洋金花和木本曼陀罗及茄科其他物种的系统发育关系。方法利用华大MGISEQ-2000PE150测序平台,双末端测序策略对基因组DNA建库测序,用NOVOPlasty组装叶绿体基因组,采用最大似然法(maximum likelihood,ML)构建系统进化树。结果洋金花和木本曼陀罗的叶绿体基因组全长为155934bp和155939bp,分别包含131和130个基因,GC值32.3%,具有典型的四分区域结构,包括1个大单拷贝区(large single copy,LSC)、1对反向重复区(inverted repeats,IR)和1个小单拷贝区(small single copy,SSC),各区域序列长度分别为86354、86278、25609、25720、18362、18221 bp。系统发育分析表明,洋金花与曼陀罗属的曼陀罗构成1单系分支,具有100%支持率,而木本曼陀罗属与曼陀罗属构成单系分支,具有100%支持率。结论结果支持洋金花隶属于曼陀罗属,与曼陀罗亲缘关系较近,木本的木曼陀罗属从曼陀罗属分出,独立为一个属。洋金花和木本曼陀罗叶绿体基因组信息为后期分子鉴定和群体遗传研究奠定基础。
基金supported by National Natural Science Foundation of China(No.81973171)Postgraduate Research&Practice Innovation Program of Jiangsu Province(Nos.KYCX20J561,SJCX200533).
文摘Natural product bufotenine(5)which could be isolated from Venenum Bufonis,has been widely used as a tool in central nervous system(CNS)studies.We present here its quaternary ammonium salt(6)which was synthesized with high yields using 5-benzyloxyindole as raw materials,and we firstly discover its analgesic effects in vivo.The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice.Moreover,the combination of compound 6 and morphine has a synergistic effect.We intended to explain the molecular mechanism of this effect.Therefore,36 analgesic-related targets(including 15 G protein-coupled receptors,6 enzymes,13 ion channels,and 2 others)were systemically evaluated using reverse docking.The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase(AChE)orα_(4)β_(2) nicotinic acetylcholine receptor(nAChR).This study provides practitioners a new insight of analgesic effects.