Objective This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma(DLBCL),a common and heterogeneous malignancy of the adult...Objective This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma(DLBCL),a common and heterogeneous malignancy of the adult lymphohematopoietic system.Given the limitations of current therapies,there is a pressing need to develop new and effective drugs for DLBCL treatment.Methods A series of pyrrolidone derivatives were synthesized,and their antitumor activities were assessed,particularly against DLBCL cell lines.Structure-activity relationship(SAR)analysis was conducted to identify key structural components essential for activity.The most promising compound,referred to as compound 7,was selected for further mechanistic studies.The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting,and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis.Results The compound 7 exhibited good antitumor activity among the synthesized derivatives,specifically in DLBCL cell lines.SAR analysis highlighted the critical role ofα,β-unsaturated ketones in the antitumor efficacy of these compounds.Mechanistically,compound 7 was found to induce significant DNA damage,trigger an inflammatory response,cause mitochondrial dysfunction,and disrupt cell cycle progression,ultimately leading to apoptosis of DLBCL cells.Conclusion The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death.These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL.展开更多
Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinq...Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinqua.Their structures were determined based on comprehensive spectroscopic and mass spectrometric analysis.The absolute configuration of 1 was determined by X-ray analysis.Compounds 1 and 2 were tested for their cytotoxic activity against five human tumor cell lines.展开更多
Objective To study the chemical constituents of whole plant of Phyllanthus urinaria and their biological activity.Methods The chemical constituents were isolated and purified by repeated column chromatography over sil...Objective To study the chemical constituents of whole plant of Phyllanthus urinaria and their biological activity.Methods The chemical constituents were isolated and purified by repeated column chromatography over silica gel,Rp-C18（reverse phase）,MCI,and Sephadex LH-20,as well as semi-preparative HPLC.NMR spectroscopic analyses were used for the structure identification.In this case,the inhibitory rate of NO production of the isolated triterpenoids was evaluated.Results Seven triterpenoids,identified as28-norlup-20（29）-ene-3,17β-diol（1）,betulin（2）,β-betulinic acid（3）,3-oxofriedelan-28-oic acid（4）,oleanolic acid（5）,3R-E-coumaroyltaraxerol（6）,and 3R-Zcoumaroyltaraxerol（7）,were isolated and identified from the whole plants of P.urinaria.Compounds 1-5 exerted inhibitory effects against NO production in LPS-induced RAW264.7 mouse macrophages with the inhibitory rate of NO production ranging from 4.0%to 27.8%at the concentration of 25 μmol/L.Conclusion To the best of our knowledge,this is the first report of compounds 1-4,6,and 7 from the family Euphorbiaceae.Compounds 1-5 exhibited inhibitory effects against NO production in LPS-induced RAW264.7 mouse macrophages.展开更多
基金financially supported by the National Natural Science Foundation of China(No.81903461)the Natural Science Foundation of Hubei Province(No.ZRMS2023000340).
文摘Objective This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma(DLBCL),a common and heterogeneous malignancy of the adult lymphohematopoietic system.Given the limitations of current therapies,there is a pressing need to develop new and effective drugs for DLBCL treatment.Methods A series of pyrrolidone derivatives were synthesized,and their antitumor activities were assessed,particularly against DLBCL cell lines.Structure-activity relationship(SAR)analysis was conducted to identify key structural components essential for activity.The most promising compound,referred to as compound 7,was selected for further mechanistic studies.The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting,and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis.Results The compound 7 exhibited good antitumor activity among the synthesized derivatives,specifically in DLBCL cell lines.SAR analysis highlighted the critical role ofα,β-unsaturated ketones in the antitumor efficacy of these compounds.Mechanistically,compound 7 was found to induce significant DNA damage,trigger an inflammatory response,cause mitochondrial dysfunction,and disrupt cell cycle progression,ultimately leading to apoptosis of DLBCL cells.Conclusion The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death.These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL.
基金the National Natural Science Foundation of China(81373290 and 21322204).
文摘Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinqua.Their structures were determined based on comprehensive spectroscopic and mass spectrometric analysis.The absolute configuration of 1 was determined by X-ray analysis.Compounds 1 and 2 were tested for their cytotoxic activity against five human tumor cell lines.
基金New Century Excellent Talents in University,State Education Ministry of China(No.NCET-2008-0224)National Natural Science Foundation of China(No.31200258,81641129)Fundamental Research Funds for Central Universities(No.2012QN012)
文摘Objective To study the chemical constituents of whole plant of Phyllanthus urinaria and their biological activity.Methods The chemical constituents were isolated and purified by repeated column chromatography over silica gel,Rp-C18（reverse phase）,MCI,and Sephadex LH-20,as well as semi-preparative HPLC.NMR spectroscopic analyses were used for the structure identification.In this case,the inhibitory rate of NO production of the isolated triterpenoids was evaluated.Results Seven triterpenoids,identified as28-norlup-20（29）-ene-3,17β-diol（1）,betulin（2）,β-betulinic acid（3）,3-oxofriedelan-28-oic acid（4）,oleanolic acid（5）,3R-E-coumaroyltaraxerol（6）,and 3R-Zcoumaroyltaraxerol（7）,were isolated and identified from the whole plants of P.urinaria.Compounds 1-5 exerted inhibitory effects against NO production in LPS-induced RAW264.7 mouse macrophages with the inhibitory rate of NO production ranging from 4.0%to 27.8%at the concentration of 25 μmol/L.Conclusion To the best of our knowledge,this is the first report of compounds 1-4,6,and 7 from the family Euphorbiaceae.Compounds 1-5 exhibited inhibitory effects against NO production in LPS-induced RAW264.7 mouse macrophages.
