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Secondary Metabolites and Their Anti-tumor Activity from Pericampylus Galucus and Three Actinomycetic Antibiotic-resistent Strains

Author: ZhaoWeiQuan
Tutor: CuiChengBin
School: PLA Military Academy of Medical Sciences
Course: Medicinal Chemistry
Keywords: Metabolite Pericampylus galucus Antibiotic-resistent ribosome-engineering Anti-tumor Actinomycetic
CLC: R284
Type: PhD thesis
Year: 2008
Downloads: 228
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Abstract


This dissertation describes the secondary metabolites and their anti-tumor activity from Pericampylus galucus and three actinomycetic antibiotic-resistent atrains.Studies include the isolation,identification and anti-tumor activities of the constituents from Pericampylus galucus,as well as the induction of a non-active actinomycetic strain,fermentation,screening of antibiotic-resistent Strains by MTT method using K562 cells and the isolation, identification and anti-tumor activities of the constituents from three actinomycetic antibiotic-resistent Strains.The front segment of dissertation is about isolation and identification of the constituents from Pericampylus galucus and their anti-tumor activities.The bronches and leaves of Pericampylus galucus has been used as a folk medicine in Yunnan province of China to cure tumor,itch,tetanus,eclampsia et al.The alcohol extract of its bronches and leaves with anticancer activity screened by MTT method showed anti-tumor activities.In order to elucidate the anti-tumor constituents,the chemical and biological investigation had been carried out.The results are fellow as:five triterpenoids 1-5 were isolated from Pericampylus glaucus and they were identified as Hopenone-B(1),hopenol-B(2),22-Hydroxyhopan-3-one (3),erythrodiol 3-palmitate(4)and 5β,24-cyclofriedelan-3-one(5);Among them,4 inhibited the proliferation of K562 cells with the inhibition rate of 47%at 100μg/mL; Compounds 1-5 were isolated from the genus Pericampylus for the first time,4 provides the first example of anti-tumor constituents of Pericampylus glaucus and its anti-tumor activity was also assayed for the first time.The rear segment of dissertation is about the method of a non-active Actinomycetic strain chosen as a original strain and induced the antibiotic resistant,isolation and identification of the constituents from three actinomycetic antibiotic-resistent Strains,preliminary evaluation for anti-tumor activities of pure compounds.A strain M15 shows no anti-tumor activities and was chosen as a original strain and then was induced the antibiotic(streptomycin,neomycin, gentamicin,Rifampicin)resistant i.e.ribosome engineering technology.63 strains of mutation were obtained,and their fermentation with anti-tumor activity screened by MTT method were examined using K562 cells.6 strains of 63 shows anti-tumor activities.3 of 6 strains having anti-tumor activities was to elucidate the anti-tumor constituents with the method of Guiding by bioassay of anti-tumor and comparing with original strain.The results are fellow as:9 compounds 6-14 were isolated and identified as uracil(6),Genistein(7),4 -(methyamino)-benzoic acid(8),1H-pyrrole-2-canboxylic acid(9),2,3-dihydrobenzoic acid (10),ergosterol peroxide(11),N-(2-hydroxyphenyl)-acetamide(12),Daidzein(13), 1,9-Dicarbomethoxy-phenazine(14).6,7,11,13 and 14 inhibited the proliferation of K562 cells with the inhibition rate of 41.4%,51.6%,28.1%,21.4%and 25.2 at 100μg/mL; Compounds 14 were isolated from the nature for the first time and its anti-tumor activity was also assayed for the first time.Above studies indicated that it is feasible to exploit new microbial resources for medicinal usage by applying the ribosome-engineering technology to non-active actinomycete in nature.

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