盐霉素类似物的分离及抑制吲哚胺2,3-双加氧酶活性研究
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摘要
为研究盐霉素发酵粗产物中的新型盐霉素类活性化合物。实验通过制备色谱从盐霉素发酵粗产物中分离得到两个盐霉素类似物,并利用波谱手段表征了这两个化合物的结构,化合物A为40-甲基盐霉素,化合物B为35-甲基盐霉素,均为新化合物。生物活性研究表明,化合物B具有一定的吲哚胺2,3-双加氧酶(IDO)抑制活性。
To study the novel salinomycin analogues in the salinomycin fermentation product,in this work,two salinomycin analogues were prepared from the salinomycin fermentation product by preparative chromatography and subsequently characterized by spectroscopic means.Compound A was found to be 40-methyl salinomycin and compound B was found to be 35-methyl salinomycin,both of the analogues were new compounds.Biological activity studies indicated that compound B exhibited inhibitory activity against indoleamine 2,3-dioxygenase(IDO).
To study the novel salinomycin analogues in the salinomycin fermentation product,in this work,two salinomycin analogues were prepared from the salinomycin fermentation product by preparative chromatography and subsequently characterized by spectroscopic means.Compound A was found to be 40-methyl salinomycin and compound B was found to be 35-methyl salinomycin,both of the analogues were new compounds.Biological activity studies indicated that compound B exhibited inhibitory activity against indoleamine 2,3-dioxygenase(IDO).
引文
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10 Blazsek M,Kubi M.HPLC determination of salinomycin and related compounds in fermentation media of Streptomyces albus and premixes[J].J Pharm Biomed Anal,2005,39:564-571.
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12 Ivanova1 J,Pantcheva IN,Mitewa M,et al.Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin[J].Chem Cent J,2011,5:52.
13 Moon YW,Hajjar J,Hwu P,et al.Targeting the indoleamine 2,3-dioxygenase pathway in cancer[J].J immunother Cancer,2015,3(6):51.
2 Yurkovich ME,Tyrakis PA,Hong H,et al.A late-stage intermediate in salinomycin biosynthesis is revealed by specific mutation in the biosynthetic gene cluster[J].Chem Bio Chem,2012,13:66-71.
3 Huczyński A,Janczak J,Antoszczak M,et al.X-ray,FT-IR,NMR and PM5 structural studies and antibacterial activity of unexpectedly stable salinomycin-benzotriazole intermediate ester[J].J Mol Struct,2012,1022:197-203.
4 Paulus EF,Kurz M,Matter H,et al.Solid-state and solution structure of the salinomycin-sodium complex:Stabilization of different conformers for an ionophore in different environments[J].J Am Chem Soc,1998,120:8209-8221.
5 Pankiewicz R.Spectroscopic and computational study of a new isomer of salinomycin[J].J Mol Struct,2013,1048:464-470.
6 Miyazaki Y,Kinashi H,Otake N,et al.Chemical modification and structure-activity correlation of salinomycin[J].J Agr Biol Chem,1976,40:1633-1640.
7 Huczynski A,Janczak J,Antoszczak M,et al.Antiproliferative activity of salinomycin and its derivatives[J].Bioorg Med Chem Lett,2012,22:7146-7150.
8 Gupta PB,Onder TT,Jiang GZ,et al.Identification of selective inhibitors of cancer stem cells by high-throughput screening[J].Cell,2009,138:645-659.
9 Huczyński A.Salinomycin-A new cancer drug candidate[J].Chem Biol Drug Des,2012,79:235-238.
10 Blazsek M,Kubi M.HPLC determination of salinomycin and related compounds in fermentation media of Streptomyces albus and premixes[J].J Pharm Biomed Anal,2005,39:564-571.
11 Davis AL,Harris JA,Russell CAL,et al.Investigations by HPLC-electrospray mass spectrometry and NMR spectroscopy into the isomerisation of salinomycin[J].Analyst,1999,124:251-256.
12 Ivanova1 J,Pantcheva IN,Mitewa M,et al.Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin[J].Chem Cent J,2011,5:52.
13 Moon YW,Hajjar J,Hwu P,et al.Targeting the indoleamine 2,3-dioxygenase pathway in cancer[J].J immunother Cancer,2015,3(6):51.