ABSTRACT
One new xanthone, griseophenexanthone A (1), one new benzophenone, digriseophene A (2), and 14 previously reported compounds were isolated from the culture of Penicillium sp. ct-28, an endophytic fungus of Corydlis tomentella. The structures of the isolated compounds were identified by an extensive analysis of HRESIMS, 1D and 2D NMR. MTT assay showed that six xanthones (1 and 3-7) significantly inhibited cell proliferation in four cancer cell lines, with IC50 values ranging from 18.12 ± 2.42 to 85.55 ± 7.66 µM. Our results showed that slight structural changes led to obvious activity differences among these compounds. We also investigated the effects of the six xanthones on cell cycle and apoptosis in human hepatoma HepG2 cells. Compound 7 caused cell cycle arrest at G1 phase, compounds 5 and 6 caused cell cycle arrest at S phase, whereas compounds 1, 3 and 4 had no effects on cell cycle distribution. All six xanthones induced apoptosis in dose-dependent manners in HepG2 cells accompanied by degradation of PARP and activation of caspase 3. The structure-activity relationship analysis revealed that the effects of these xanthones on cell cycle and apoptosis in HepG2 cells were closely related to the substituent groups on their skeleton. Our studies provide novel insights for the structural optimization of xanthones in the development of new anticancer drugs.
Subject(s)
Benzophenones/toxicity , Cell Proliferation/drug effects , Corydalis/microbiology , Penicillium/chemistry , Xanthones/toxicity , Apoptosis/drug effects , Benzophenones/chemistry , Benzophenones/isolation & purification , Cell Cycle/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Structure-Activity Relationship , Xanthones/chemistry , Xanthones/isolation & purificationABSTRACT
Two Gram-stain positive, aerobic actinomycete strains, designated NEAU-YHS12 and NEAU-YHS15(T), were isolated from the root of Corydalis yanhusuo L. collected from Wuchang, Heilongjiang Province, northeast China. Phylogenetic analysis of 16S rRNA gene sequences showed that the two strains are closely related to one another (99.8 % similarity), and had the closest relationship with Sphaerisporangium cinnabarinum JCM 3291(T) (98.7, 98.6 %), Sphaerisporangium flaviroseum YIM 48771(T) (98.6, 98.6 %), Sphaerisporangium melleum JCM 13064(T) (98.5, 98.4 %) and Sphaerisporangium dianthi NEAU-CY18(T) (98.4, 98.4 %). DNA-DNA hybridization value between strains NEAU-YHS12 and NEAU-YHS15(T) was 82 ± 1.4 %, and the values between the two strains and the closely related type strains were well below 70 %. The two strains also shared a number of phenotypic characteristics that were distinct from the closely related species. Both strains were observed to contain MK-9(H6), MK-9(H4) and MK-9(H2) as the detected menaquinones. The cell wall peptidoglycan was found to contain meso-diaminopimelic acid. The phospholipid profiles were found to contain diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, phosphoglycolipid, and an unidentified phospholipid. The major fatty acids were identified as iso-C16:0, C17:1 ω7c, C18:0 and iso-C15:0. On the basis of the genetic and phenotypic properties, it is proposed that strains NEAU-YHS15(T) and NEAU-YHS12 be classified as representatives of a novel species of the genus Sphaerisporangium, for which the name Sphaerisporangium corydalis sp. nov is proposed. The type strain is NEAU-YHS15(T) (CGMCC 4.7148(T) = DSM46732(T)).
Subject(s)
Actinobacteria/classification , Actinobacteria/isolation & purification , Corydalis/microbiology , Actinobacteria/genetics , Actinobacteria/physiology , Aerobiosis , Cell Wall/chemistry , China , Cluster Analysis , Cytosol/chemistry , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Diaminopimelic Acid/analysis , Fatty Acids/analysis , Molecular Sequence Data , Nucleic Acid Hybridization , Peptidoglycan/analysis , Phospholipids/analysis , Phylogeny , Plant Roots/microbiology , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/analysisABSTRACT
(+/-)-alpha-Hydrastine and (+/-)-beta-hydrastine were isolated from Corydalis longipes; both exhibited considerable efficacy against spore germination of some saprophytic and phytopathogenic fungi. While (+/-)-alpha-hydrastine was effective against most of the fungi, Helminthosporium echinoclova was least affected even at the highest dose (150 ppm). (+/-)-beta-Hydrastine was equally effective against several fungi. Mixture of both compounds was more effective than each one individually. Helminthosporium species were again the most resistant toward the mixture. The effect of both alkaloids independently on germination and development of E. pisi conidia on excised pea leaves was also shown. After pre-inoculation with (+/-)-alpha-hydrastine, the effect was more pronounced than the addition post-inoculation; maximum inhibition occurred at 200 ppm. (+/-)-beta-Hydrastine also reduced germination of conidia but was less effective than (+/-)-alpha-hydrastine. The number of primary and secondary branches of conidia and number of appressoria were not affected significantly by either compound.
