Font Size: a A A

Study On The Secondary Metabolites Produced By Streptomyces Sp. Strain NOV-0827

Posted on:2015-04-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y ChangFull Text:PDF
GTID:2284330422987699Subject:Medicinal chemistry
Abstract/Summary:PDF Full Text Request
In this study, the secondary metabolites of Streptomyces sp. NOV-0827wereisolated to screen compounds with novel structures or new bioactivity.Hsp90have attracted much attention as molecular targets of anti-cancer drugs.Especially, drug screening focuses on the Hsp90C-terminal inhibitors of lowertoxicity. This study found that a class of compounds with anti-tumor activity insecondary metabolites produced by Streptomyces sp. NOV-0827. The results showthat the active components contained coumarin compounds by TLC, and identified asnovobiocin combined with HPLC and HPLC-MSn. Further research works includeinvestigating and optimizing the fermentation conditions of the NOV-0827. Threecompounds NOV-0827-A、NOV-0827-B and NOV-0827-C were isolated from thefermentation broth of secondary metabolites produced by Streptomyces sp. NOV-0827by serial processes such as macroporous resin column chromatography, silica gelchromatography, C18chromatography, Sephadex LH-20gel column chromatography,and HPLC et al. The chemical structures of these three compounds determined by UV,IR, MS and NMR spectra were identified as aminocoumarin antibioticsnovobiocin(A), macrocyclic lactam antibiotic GT-32A(B), and GT-32B(C). Theantitumor activity of these compound were tested by MTT assay. Studies shows thatboth compound B and C have strong growth inhibitory activity of SW620cell, withIC50values=1.107μmol/mL and5.358μmol/mL respectively.Studies shows that novobiocin and two macrocyclic lactam compounds withantitumor activity are isolated from secondary metabolites produced by the samestrain of terrestrial Streptomyces. Both the macrocyclic lactam compounds havestrong antitumor activities and could be new natural chemotherapeutic candidatedrugs with for cancer therapy. Many studies have shown that novobiocin is the Hsp90C-terminal inhibitor with anti-cancer and regulating effects, and can be used withother anti-cancer drugs.
Keywords/Search Tags:Streptomyces, Novobiocin, Optimization of fermentation, Isolation and purification, Structural identification, Antitumor activity
PDF Full Text Request
Related items