Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agen...Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.展开更多
Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola,and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention.Thi...Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola,and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention.This review summarizes the progress of recent research on the antiproliferative activities of salidroside and its effects on breast,ovarian,cervical,colorectal,lung,liver,gastric,bladder,renal,and skin cancer as well as gliomas and fibrosarcomas.Thus,it provides a reference for the further development and utilization of salidroside.展开更多
Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. ...Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8 a(IC50=3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound 15 u(IC50=49 nmol/L, and Ki= 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3 K4 me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency ofcompound 15 u. Compound 15 u also showed strong antiproliferative activity against four leukemia cell lines(OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, 15 u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15 u induced expression of CD86 and CD11 b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation.The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazolefused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1 A inhibitors.展开更多
A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line （H...A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line （HL-60）, human lung adenocarcinoma epithelial cell line （A549） and human breast cancer cell line （MDA-MB-231） in vitro by standard MTT assay. The pharmacological results indicated that some compounds exhibited promising antitumor activities. Compound 1j showed the most potent antiproliferative activity against the tested three cell lines with IC50 values of 0.13 μmol/L, 0.7 μmol/L and 0.5μmol/L, respectively.展开更多
To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODSChanges in cell proliferation and the cytotoxic effect of the test...To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODSChanges in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining. The flow cytometry method also allowed us to measure changes in levels or activation states of other factors associated with apoptosis, such as poly (ADP-ribose) polymerase (PARP), caspase-3 and -9, cytochrome c, Bcl-2 family proteins, and also the integrity of the mitochondrial membrane. To evaluate activity of the transcription factors and proteins involved in signaling pathways we used Western blot analysis together with flow cytometry. RESULTSAmong the ten tested compounds, compound K-453 {(±)-trans-1,2-dimethoxy-2’-(3,5-bis-trifluoromethylphenylamino)spiro{indoline-3,5’[4’,5’]dihydrothiazol} exhibited the most potent activity with IC<sub>50</sub> = 32.22 ± 1.14 μmol/L in human colorectal HCT116 cells and was thus selected for further studies. Flow cytometric analysis revealed a K-453-induced increase in the population of cells with sub-G<sub>1</sub> DNA content, which is considered as a marker of apoptotic cell death. The apoptosis-inducing effect of compound K453 was also confirmed by annexin V/PI double staining and AO/PI staining. The apoptosis was associated with the loss of mitochondrial membrane potential, PARP cleavage, caspase-3 and caspase-9 activation, release of cytochrome c, as well as changes in the levels of Bcl-2 family members. Moreover, flow cytometry showed that compound K-453 stimulates phosphorylation of p38 MAPK but decreases phosphoryla展开更多
The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature....The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.展开更多
Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antip...Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antiproliferative activity.Methods:The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120,silica gel,Sephadex LH-20,and HPLC.The structures of compounds were determined by 1D,2D NMR,and HR-ESI-MS data.The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase(LDH)procedure.The antiproliferative activity was evaluated using MTT assay.Results:The study led to the isolation of 23 compounds,including one new compound,identified as(2Z)-3-[4-(β-D-glucopyranosyloxy)-2′-hydroxy-5′-methoxyphenyl]-2-propenoic acid(1),together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile(2),methyl 4-methoxynicotinate(3),4-methoxynicotinonitrile(4),1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone(5),neoisoastilbin(6),isoastilbin(7),aromadendrin(8),neoastilbin(9),astilbin(10),quercitrin(11),neoschaftoside(12),apigenin 6,8-bis-C-α-L-arabinoside(13),vitexin(14),bergenin(15),scopoletin(16),glucopyranoside salicyl(17),koaburside(18),benzylβ-D-glucoside(19),icariside B5(20),roseoside(21),loliolide(22),and adenosine(23).The tested compounds did not show LDH inhibition nor antiproliferative activity.Conclusion:Compound 1 was a new glycoside.Compounds 2 and 3 were obtained for the first time from natural source.The 22 known compounds constituted of alkaloids(2–4,23),phenolics(5,15,17,18),flavonoids(6–14),coumarin(16),benzyl glycoside(19),and norsesquiterpenes(20–22).All the compounds,1–23,were revealed from M.hemsleyana for the first time.This is the initial uncovering of molecules 1–10,12,13,17–19,and 23 from the genus Macaranga.The isolated compounds,11,14–16,and 20–22 established taxonomic classification of M.hemsleyana in Euphorbiaceae family.Flavonoids were outstanding as chemosystematic markers展开更多
Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine...Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine,O-methylthreonine,hexahydropyridazine-3-carboxylic acid,5-hydroxytetrahydropyridazine-3-carboxylic acid,and(2S,3R,4E,6E)-2-amino-3–hydroxy-4,6-dienoic acid residues.Pyridapeptide I(4)contains(2S,3R,4E,6E)-2-amino-3–hydroxy-8-methylnona-4,6-dienoic acid residue and a very rare glycose residue,aculose.Their structures were determined based on spectroscopic analysis and chemical methods.Pyridapeptides G–I(2–4)have the 2,3,6-trideoxyhexose units glycosylated at theγ-OH-TPDA residue,displayed significant antiproliferative activity against four(PC9,MKN45,Hep G2,K562)or two(PC9,MKN45)human cancer cell lines.展开更多
Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives ha...Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives has never been reported.Herein,we report the total synthesis of cajanine in nine steps with an overall yield of 10%together with its analog,longistyline A,in 8%yield.The antiproliferative activity of the two compounds against a human hepatoma cell line is also reported.展开更多
Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work,...Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work, novel vinyl dipeptides which are different in a double bond between the α-carbon of peptide and C1 of its side chain. Added to that, suitable substituents were selected to harness drug-like properties. The compounds were found to have moderate activities when tested against MCF-7 breast cancer cell line. For instance, the adamantyl analogue 2-(benzoylamino)-3-(2-furyl)-N-(1-adamantyl) propenamide (1c) and the heterocyclic analogue 2-(Benzoylamino)-3-(2-furyl)-N-[2-(5-cyanothia-zol-2-yl)] propenamide (1o) exhibited inhibition potency at 27.4 and 37.8 μM, respectively.展开更多
A series of novel sorafenib derivatives have been designed and synthesized.The cytotoxic activities of these compounds were tested in three tumor cell lines.Most of the compounds showed potent antiproliferative activi...A series of novel sorafenib derivatives have been designed and synthesized.The cytotoxic activities of these compounds were tested in three tumor cell lines.Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50= 0–20 mmol/L.Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines.Among them,compound 5g demonstrated significant inhibitory activity against A549,ACHN and MDAMB-231 cell lines with IC50values of 1.29,1.99,3.11 mmol/L,respectively.展开更多
In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids(Mito HCAs) were synthesized by conjugation with a...In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids(Mito HCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OH? àand ROO? àinduced lipid peroxidation. H_2O_2 production was decreased significantly by increasing glutathione peroxidase and catalase activities. In addition, cell proliferation data from three cell lines(HepG2, L02 and WI38) indicated that the Mito HCAs were selective for cancer cells. Interestingly, the Mito HCAs both with or without Ca^(2+)triggered mitochondrial dysfunction by inducing mitochondrial swelling, collapsing the mitochondrial membrane potential and causing cytochrome c release. In particular, an inhibitor of the mitochondrial permeability transition pore(m PTP), cyclosporin A, attenuated mitochondrial damage and cell apoptosis, indicating that m PTP may be involved in the antiproliferative activity of Mito HCAs.Further studies focused on structural optimization of these compounds are onging.展开更多
Soybean isoflavones have been one of the potential preventive candidates for antitumor research in recent years. In this paper, we first studied the transformation of soybean isoflavones with the homogenized slurry of...Soybean isoflavones have been one of the potential preventive candidates for antitumor research in recent years. In this paper, we first studied the transformation of soybean isoflavones with the homogenized slurry of Ganoderma lucidum. The resultant transformed products（TSI） contained（703.21±4.35） mg/g of genistein, with transformed rates of 96.63% and 87.82% of daidzein and genistein, respectively, and TSI also could enrich the bioactive metabolites of G. lucidum. The antitumor effects of TSI on human colorectal cancer cell line HTL-9, human breast cancer cell line MCF-7, and human immortalized gastric epithelial cell line GES-1 were also studied. The 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide（MTT） assay showed that TSI could dramatically reduce the viability rates of HTL-9 cells and MCF-7 cells without detectable cytotoxicity on GES-1 normal cells when the TSI concentration was lower than 100 μg/ml. With 100 μg/ml of TSI, HTL-9 cells were arrested in the G1 phase, and late-apoptosis was primarily induced, accompanied with partial early-apoptosis. TSI could induce primarily earlyapoptosis by arresting cells in the G1 phase of MCF-7 cells. For HTL-9 cells, Western-blot and reverse-transcriptase polymerase chain reaction（RT-PCR） analysis showed that TSI（100 μg/ml） can up-regulate the expression of Bax, Caspase-3, Caspase-8, and cytochrome c（Cyto-c）, indicating that TSI could induce cell apoptosis mainly through the mitochondrial pathway. In addition, the expression of p53 was up-regulated, while the expression of Survivin and nuclear factor κB（NF-κB） was down-regulated. All these results showed that TSI could induce apoptosis of HTL-9 cells by the regulation of multiple apoptosis-related genes.展开更多
文摘Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.
文摘Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola,and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention.This review summarizes the progress of recent research on the antiproliferative activities of salidroside and its effects on breast,ovarian,cervical,colorectal,lung,liver,gastric,bladder,renal,and skin cancer as well as gliomas and fibrosarcomas.Thus,it provides a reference for the further development and utilization of salidroside.
基金supported by the National Key Research Program of Proteins(Nos.2016YFA0501800 and 2017YFD0501401,China)the National Natural Science Foundation of China(Nos.81703326,81773562,81430085 and 21403200,China)+5 种基金the Open Fund of State Key Laboratory of Pharmaceutical Biotechnology,Nan-jing University,China(No.KF-GN-201902,China)Outstanding Young Talent Research Fund of Zhengzhou University(No.1521331002,China)Scientific Program of Henan Province(Nos.182102310123 and 161100310100,China)China Postdoctoral Science Foundation(No.2018M630840,China)Key Research Program of Higher Education of Henan Province(Nos.15A350018 and 18B350009,China)the Starting Grant of Zhengzhou University(No.32210533,China)
文摘Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8 a(IC50=3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound 15 u(IC50=49 nmol/L, and Ki= 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3 K4 me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency ofcompound 15 u. Compound 15 u also showed strong antiproliferative activity against four leukemia cell lines(OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, 15 u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15 u induced expression of CD86 and CD11 b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation.The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazolefused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1 A inhibitors.
基金supported by the National High Technology Research and Development Program (‘‘863’’ Program)of China (No. 2012AA020305)National Natural Science Foundation of China (No. 21002065)Shenyang Scienceand Technology Plan Projects (No. F11-151-9-00)
文摘A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line （HL-60）, human lung adenocarcinoma epithelial cell line （A549） and human breast cancer cell line （MDA-MB-231） in vitro by standard MTT assay. The pharmacological results indicated that some compounds exhibited promising antitumor activities. Compound 1j showed the most potent antiproliferative activity against the tested three cell lines with IC50 values of 0.13 μmol/L, 0.7 μmol/L and 0.5μmol/L, respectively.
文摘To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODSChanges in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining. The flow cytometry method also allowed us to measure changes in levels or activation states of other factors associated with apoptosis, such as poly (ADP-ribose) polymerase (PARP), caspase-3 and -9, cytochrome c, Bcl-2 family proteins, and also the integrity of the mitochondrial membrane. To evaluate activity of the transcription factors and proteins involved in signaling pathways we used Western blot analysis together with flow cytometry. RESULTSAmong the ten tested compounds, compound K-453 {(±)-trans-1,2-dimethoxy-2’-(3,5-bis-trifluoromethylphenylamino)spiro{indoline-3,5’[4’,5’]dihydrothiazol} exhibited the most potent activity with IC<sub>50</sub> = 32.22 ± 1.14 μmol/L in human colorectal HCT116 cells and was thus selected for further studies. Flow cytometric analysis revealed a K-453-induced increase in the population of cells with sub-G<sub>1</sub> DNA content, which is considered as a marker of apoptotic cell death. The apoptosis-inducing effect of compound K453 was also confirmed by annexin V/PI double staining and AO/PI staining. The apoptosis was associated with the loss of mitochondrial membrane potential, PARP cleavage, caspase-3 and caspase-9 activation, release of cytochrome c, as well as changes in the levels of Bcl-2 family members. Moreover, flow cytometry showed that compound K-453 stimulates phosphorylation of p38 MAPK but decreases phosphoryla
基金supported by the National Natural Science Foundation of China(82274085)the Natural Science Foundation of Jiangsu Province(BK20220478)the Natural Science Foundation of Jiangsu Higher Education institutions of China(22KJB360010).
文摘The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.
基金supported by the National Natural Science Foundation of China(No.81860615,82260682)Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(No.2022YKZY001).
文摘Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antiproliferative activity.Methods:The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120,silica gel,Sephadex LH-20,and HPLC.The structures of compounds were determined by 1D,2D NMR,and HR-ESI-MS data.The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase(LDH)procedure.The antiproliferative activity was evaluated using MTT assay.Results:The study led to the isolation of 23 compounds,including one new compound,identified as(2Z)-3-[4-(β-D-glucopyranosyloxy)-2′-hydroxy-5′-methoxyphenyl]-2-propenoic acid(1),together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile(2),methyl 4-methoxynicotinate(3),4-methoxynicotinonitrile(4),1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone(5),neoisoastilbin(6),isoastilbin(7),aromadendrin(8),neoastilbin(9),astilbin(10),quercitrin(11),neoschaftoside(12),apigenin 6,8-bis-C-α-L-arabinoside(13),vitexin(14),bergenin(15),scopoletin(16),glucopyranoside salicyl(17),koaburside(18),benzylβ-D-glucoside(19),icariside B5(20),roseoside(21),loliolide(22),and adenosine(23).The tested compounds did not show LDH inhibition nor antiproliferative activity.Conclusion:Compound 1 was a new glycoside.Compounds 2 and 3 were obtained for the first time from natural source.The 22 known compounds constituted of alkaloids(2–4,23),phenolics(5,15,17,18),flavonoids(6–14),coumarin(16),benzyl glycoside(19),and norsesquiterpenes(20–22).All the compounds,1–23,were revealed from M.hemsleyana for the first time.This is the initial uncovering of molecules 1–10,12,13,17–19,and 23 from the genus Macaranga.The isolated compounds,11,14–16,and 20–22 established taxonomic classification of M.hemsleyana in Euphorbiaceae family.Flavonoids were outstanding as chemosystematic markers
基金financially supported by the National Natural Science Foundation of China(No.U1906213)the National Key Research and Development Program of China(No.2022YFC2804100)。
文摘Four new cyclohexapeptides,pyridapeptides F–I(1–4),were isolated from the fermentation broth of marine sponge-derived Streptomyces sp.OUCMDZ-4539.The pyridapeptides F–H(1–3)are composed ofβ-hydroxyleucine,alanine,O-methylthreonine,hexahydropyridazine-3-carboxylic acid,5-hydroxytetrahydropyridazine-3-carboxylic acid,and(2S,3R,4E,6E)-2-amino-3–hydroxy-4,6-dienoic acid residues.Pyridapeptide I(4)contains(2S,3R,4E,6E)-2-amino-3–hydroxy-8-methylnona-4,6-dienoic acid residue and a very rare glycose residue,aculose.Their structures were determined based on spectroscopic analysis and chemical methods.Pyridapeptides G–I(2–4)have the 2,3,6-trideoxyhexose units glycosylated at theγ-OH-TPDA residue,displayed significant antiproliferative activity against four(PC9,MKN45,Hep G2,K562)or two(PC9,MKN45)human cancer cell lines.
基金The authors gratefully acknowledge financial support from the National Natural Science Foundation of China(Grant 30772646)the National Major Science and Technology Project of China("Innovation and Development of New Drugs",Grant 2009ZX09102-065).
文摘Cajanine,a constituent of Cajanaus cajan L.,used in traditional Chinese medicine,is a promising drug candidate because of its broad range of bioactivities.However,the total synthesis of cajanine and its derivatives has never been reported.Herein,we report the total synthesis of cajanine in nine steps with an overall yield of 10%together with its analog,longistyline A,in 8%yield.The antiproliferative activity of the two compounds against a human hepatoma cell line is also reported.
文摘Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work, novel vinyl dipeptides which are different in a double bond between the α-carbon of peptide and C1 of its side chain. Added to that, suitable substituents were selected to harness drug-like properties. The compounds were found to have moderate activities when tested against MCF-7 breast cancer cell line. For instance, the adamantyl analogue 2-(benzoylamino)-3-(2-furyl)-N-(1-adamantyl) propenamide (1c) and the heterocyclic analogue 2-(Benzoylamino)-3-(2-furyl)-N-[2-(5-cyanothia-zol-2-yl)] propenamide (1o) exhibited inhibition potency at 27.4 and 37.8 μM, respectively.
基金provided by the National S&T Major Special Project on Major New Drug Innovation (No. 2012ZX09103-101-019)
文摘A series of novel sorafenib derivatives have been designed and synthesized.The cytotoxic activities of these compounds were tested in three tumor cell lines.Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50= 0–20 mmol/L.Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines.Among them,compound 5g demonstrated significant inhibitory activity against A549,ACHN and MDAMB-231 cell lines with IC50values of 1.29,1.99,3.11 mmol/L,respectively.
基金supported by the National Natural Sciences Foundation of China (Grant No. 21302079)the Fundamental Research Funds for the Central Universities (No. lzujbky2014151)
文摘In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids(Mito HCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OH? àand ROO? àinduced lipid peroxidation. H_2O_2 production was decreased significantly by increasing glutathione peroxidase and catalase activities. In addition, cell proliferation data from three cell lines(HepG2, L02 and WI38) indicated that the Mito HCAs were selective for cancer cells. Interestingly, the Mito HCAs both with or without Ca^(2+)triggered mitochondrial dysfunction by inducing mitochondrial swelling, collapsing the mitochondrial membrane potential and causing cytochrome c release. In particular, an inhibitor of the mitochondrial permeability transition pore(m PTP), cyclosporin A, attenuated mitochondrial damage and cell apoptosis, indicating that m PTP may be involved in the antiproliferative activity of Mito HCAs.Further studies focused on structural optimization of these compounds are onging.
文摘Soybean isoflavones have been one of the potential preventive candidates for antitumor research in recent years. In this paper, we first studied the transformation of soybean isoflavones with the homogenized slurry of Ganoderma lucidum. The resultant transformed products（TSI） contained（703.21±4.35） mg/g of genistein, with transformed rates of 96.63% and 87.82% of daidzein and genistein, respectively, and TSI also could enrich the bioactive metabolites of G. lucidum. The antitumor effects of TSI on human colorectal cancer cell line HTL-9, human breast cancer cell line MCF-7, and human immortalized gastric epithelial cell line GES-1 were also studied. The 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide（MTT） assay showed that TSI could dramatically reduce the viability rates of HTL-9 cells and MCF-7 cells without detectable cytotoxicity on GES-1 normal cells when the TSI concentration was lower than 100 μg/ml. With 100 μg/ml of TSI, HTL-9 cells were arrested in the G1 phase, and late-apoptosis was primarily induced, accompanied with partial early-apoptosis. TSI could induce primarily earlyapoptosis by arresting cells in the G1 phase of MCF-7 cells. For HTL-9 cells, Western-blot and reverse-transcriptase polymerase chain reaction（RT-PCR） analysis showed that TSI（100 μg/ml） can up-regulate the expression of Bax, Caspase-3, Caspase-8, and cytochrome c（Cyto-c）, indicating that TSI could induce cell apoptosis mainly through the mitochondrial pathway. In addition, the expression of p53 was up-regulated, while the expression of Survivin and nuclear factor κB（NF-κB） was down-regulated. All these results showed that TSI could induce apoptosis of HTL-9 cells by the regulation of multiple apoptosis-related genes.
