共查询到20条相似文献,搜索用时 15 毫秒
1.
The aim of this study is to investigate the effect of evodiamine on fibroblast activation in cardiac fibroblasts and endothelial to mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Neonatal rat cardiac fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1) to induce fibroblast activation. After co-cultured with evodiamine (5, 10 μM), the proliferation and pro-fibrotic proteins expression of cardiac fibroblasts were evaluated. HUVECs were also stimulated with TGF-β1 to induce EndMT and treated with evodiamine (5, 10 μM) at the same time. The EndMT response in the HUVECs was evaluated as well as the capacity of the transitioned endothelial cells migrating to surrounding tissue. As a result, Evodiamine-blunted TGF-β1 induced activation of cardiac fibroblast into myofibroblast as assessed by the decreased expressions of α-SMA. Furthermore, evodiamine reduced the increased protein expression of fibrosis markers in neonatal and adult rat cardiac fibroblasts induced by TGF-β1. HUVECs stimulated with TGF-β1 exhibited lower expression levels of CD31, CD34, and higher levels of α-SMA, vimentin than the control cells. This phenotype was eliminated in the HUVECs treated with both 5 and 10 μM evodiamine. Evodiamine significantly reduced the increase in migration ability that occurred in response to TGF-β1 in HUVECs. In addition, the activation of Smad2, Smad3, ERK1/2, and Akt, and the nuclear translocation of Smad4 in both cardiac fibroblasts and HUVEC were blocked by evodiamine treatment. Thus, evodiamine could prevent cardiac fibroblasts from activation into myofibroblast and protect HUVEC against EndMT. These effects may be mediated by inhibition of the TGFβ pathway in both cardiac fibroblasts and HUVECs. 相似文献
2.
Cesar A. Meschiari Tatiane Izidoro-Toledo Raquel F. Gerlach Jose E. Tanus-Santos 《Molecular and cellular biochemistry》2013,372(1-2):127-135
Cardiovascular diseases involve critical mechanisms including impaired nitric oxide (NO) levels and abnormal matrix metalloproteinase (MMP) activity. While NO downregulates MMP expression in some cell types, no previous study has examined whether NO downregulates MMP levels in endothelial cells. We hypothesized that NO donors could attenuate MMP-9 production by human umbilical vein endothelial cells (HUVECs) as a result of less NFκB activation or cyclic GMP (cGMP)-mediated mechanisms. We studied the effects of DetaNONOate (10–400 μM) or SNAP (50–400 μM) on phorbol 12-myristate 13-acetate (PMA; 10 nM)-induced increases in MMP-9 activity (by gel zymography) or concentrations (by ELISA) as well as on a tissue inhibitor of MMPs’ (TIMP)-1 concentrations (by ELISA) in the conditioned medium of HUVECs incubated for 24 h with these drugs. We also examined whether the irreversible inhibitor of soluble guanylyl cyclase ODQ modified the effects of SNAP or whether 8-bromo-cGMP (a cell-permeable analog of cGMP) influenced PMA-induced effects on MMP-9 expression. Total and phospho-NFκB p65 concentrations were measured in HUVEC lysates to assess NFκB activation. Both NO donors attenuated PMA-induced increases in MMP-9 activity and concentrations without significantly affecting TIMP-1 concentrations. This effect was not modified by ODQ, and 8-bromo-cGMP did not affect MMP-9 concentrations. While PMA increased phospho-NFκB p65 concentrations, SNAP had no influence on this effect. In conclusion, this study shows that NO donors may attenuate imbalanced MMP expression and activity in endothelial cells independent of cGMP- or NFκB-mediated mechanisms. Our results may offer an important pharmacological strategy to approach cardiovascular diseases. 相似文献
3.
Jiangying Cao Chunhua Ma Jie Zang Shuai Gao Qianwen Gao Xiujie Kong Yugang Yan Xuewu Liang Qinge Ding Chunlong Zhao Binghe Wang Wenfang Xu Yingjie Zhang 《Bioorganic & medicinal chemistry》2018,26(12):3145-3157
The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089?±?0.007?μM, which was two orders of magnitude lower than that of bestatin (IC50?=?9.4?±?0.5?μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10?μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100?μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model. 相似文献
4.
Jinyu Yang Gaoliang Cheng Qihao Xu Shenglin Luan Shuxiang Wang Dan Liu Linxiang Zhao 《Bioorganic & medicinal chemistry》2018,26(8):1418-1425
In recent years, inhibition of HDAC6 became a promising therapeutic strategy for the treatment of cancer and HDAC6 inhibitors were considered to be potent anti-cancer agents. In this work, celecoxib showed moderate degree of HDAC6 inhibition activity and selectivity in preliminary enzyme inhibition activity assay. A series of hydroxamic acid derivatives bearing phenylpyrazol moiety were designed and synthesized as HDAC6 inhibitors. Most compounds showed potent HDAC6 inhibition activity. 11i was the most selective compound against HDAC6 with IC50 values of 0.020 µM and selective factor of 101.1. Structure-activity relationship analysis indicated that locating the linker group at 1′ of pyrazol gave the most selectivity. The most compounds 11i (GI50 = 3.63 μM) exhibited 6-fold more potent than vorinostat in HepG2 cells. Considering of the high selectivity against HDAC6 and anti-proliferation activity, such compounds have potential to be developed as anti-cancer agents. 相似文献
5.
Qing-Kun Shen Chuan-Feng Liu Hong-Jian Zhang Yu-Shun Tian Zhe-Shan Quan 《Bioorganic & medicinal chemistry letters》2017,27(21):4871-4875
Two series of xanthotoxin-triazole derivatives were designed, synthesized, and studied for their antiproliferative properties. The in vitro cytotoxicity of the compounds in the AGS cancer cell line and the L02 normal cell line was evaluated via MTT assay. Among the synthesized compounds, 9-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-7H-furo[3,2-g]chromen-7-one (6p) was found to have the greatest antiproliferative activity against AGS cells (IC50 = 7.5 μM) and showed better activity than the lead compound (xanthotoxin, IC50 > 100 μM) and the reference drug (5-fluorouracil, IC50 = 29.6 μM) did. The IC50 value of 6p in L02 cells was 13.3 times higher than that in the AGS cells. Therefore, the compound exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil. Cell cycle analysis revealed that compound 6p inhibited cell growth via the induction of S/G2 phase arrest in AGS cells. Compound 6p was identified as a promising lead compound for the further development and identification of 1,2,3-triazole-based anticancer agents. 相似文献
6.
7.
Yuanying Fang Rikang Wang Mingzhen He Hesong Huang Qi Wang Zunhua Yang Yan Li Shilin Yang Yi Jin 《Bioorganic & medicinal chemistry letters》2017,27(1):98-101
A series of nitric oxide (NO) donating derivatives of hederacolchiside A1 bearing triterpenoid saponin motif were designed, synthesized and evaluated for their anticancer activity. All of the tested furoxan-based NO releasing compounds showed significant proliferation inhibitory activities. Especially compound 6a exhibited strong cytotoxicity (IC50 = 1.6–6.5 μM) against four human tumor cell lines (SMMC-7721, NCI-H460, U251, HCT-116) in vitro and the highest level of NO releasing. Furthermore, compound 6a was revealed low acute toxicity to mice and weak haemolytic activity with potent tumor growth inhibition against mice H22 hepatocellular cells in vivo (51.5%). 相似文献
8.
Meihua Zheng Weili Qiao Jie Cui Lei Liu Hong Liu Zhirong Wang Changdong Yan 《Molecular and cellular biochemistry》2014,393(1-2):59-67
The present study was designed to investigate the effect of hydrogen sulfide on cellular senescence of human umbilical vascular endothelial cells (HUVECs CC-2517) and its underlying mechanism. The premature senescence-like phenotype HUVECs (the fourth passage) was induced by treatment with nicotinamide (NAM, an inhibitor of SIRT1, 5 mmol/L, 12 h). Cells were cultured with sodium hydrosulfide (NaHS, 12.5, 25, 50 and 100 μmol/L) for 48 h in premature senescence-like phenotype HUVECs. The fourth passage of HUVECs was considered as young group. Senescence-associated (SA)-β-galactosidase activities were detected to evaluate cell senescence, and the expression of SA heterochromatin foci (SAHF) was visualized by DAPI DNA staining. The mRNA and protein levels of SIRT1 were detected using RT-PCR and western blotting analysis, respectively. The results showed that β-galactosidase positive cells and the formation of SAHF were markedly increased after treatment with NAM (5 mmol/L) for 12 h. We also found that NaHS (12.5 μmol/L) had no effect on the percentage of SA β-gal positive cells and the expression of SAHF, and the hallmarks decreased at the concentration of 25 and 50 μmol/L, reaching the minimum at 50 μmol/L, while the percentage of SA β-gal positive cells and the expression of SAHF increased at the concentration of 100 μmol/L. Furthermore, we found that both on protein and mRNA levels of SIRT1 in the Y+N+S50 group was significantly increased compared with that in Y+N group. In conclusion, NaHS delays senescence of HUVECs induced by NAM via upregulation of SIRT1 expression. 相似文献
9.
Kalpa Wishvajith Samarakoon Kwon O-Nam Ju-Young Ko Ji-Hyeok Lee Min-Cheol Kang Daekyung Kim Joon Baek Lee Jung-Suck Lee You-Jin Jeon 《Journal of applied phycology》2013,25(5):1595-1606
Isolation of bioactive compounds and commercialization of marine microalgae sources are interesting targets in future marine biotechnology. Cultured biomass of the marine microalga, Nannochloropsis oculata, was used to purify angiotensin-I converting enzyme (ACE) inhibitory peptides using proteases including pepsin, trypsin, α-chymotrypsin, papain, alcalase, and neutrase. The pepsin hydrolysate exhibited the highest ACE inhibitory activity, compared to the other hydrolysates and then was separated into three fractions (F1, F2, and F3) using Sephadex G-25 gel filtration column chromatography. First fraction (F1) showed the highest ACE inhibitory activity and it was further purified into two fractions (F1-1 and F1-2) using reverse-phase high-performance liquid chromatography. The IC50 value of purified ACE inhibitory peptides were 123 and 173 μM and identified as novel peptides, Gly-Met-Asn-Asn-Leu-Thr-Pro (GMNNLTP; MW, 728 Da) and Leu-Glu-Gln (LEQ; MW, 369 Da), respectively. In addition, nitric oxide production level (%) was significantly increased by the purified peptide (Gly-Met-Asn-Asn-Leu-Thr-Pro) compared to the purified peptide (Leu-Glu-Gln) and other treated pepsin hydrolysate fractions on human umbilical vein endothelial cells (HUVECs). Cell viability assay showed no cytotoxicity on HUVECs with the treated purified peptides and fractions. These results suggest that the isolated peptides from cultured marine microalga, N. oculata protein sources may have potentiality to use commercially as ACE inhibitory agents in functional food industry. 相似文献
10.
Anti-breast cancer and anti-angiogenic potential of a lichen-derived small-molecule: barbatolic acid
Mehmet Varol 《Cytotechnology》2018,70(6):1565-1573
Natural products have been used for centuries as the most potent remedies to cure many diseases including cancer diseases. Angiogenesis is defined as the formation of new capillaries from existing vessels and plays a key role in the tumorigenesis process. Barbatolic acid is a little known lichen-derived small-molecule. In the present study, barbatolic acid was isolated from the acetone extract of Bryoria capillaris, and its anti-breast cancer and anti-angiogenic potential was investigated using human umbilical vein endothelial cells (HUVECs), human breast ductal carcinoma (T-47D) and cisplatin-resistant BRCA2-mutated human breast TNM stage IV adenocarcinoma (HCC1428) cells. AlamarBlue? cell viability, lactate dehydrogenase cellular membrane degradation and PicoGreen? dsDNA quantitation assays were performed to determine the cytotoxic potential of barbatolic acid. Anti-angiogenic and anti-migratory activities were investigated using endothelial tube formation assay and scratch wound healing assay, respectively. Half maximal inhibitory concentration of barbatolic acid was found to be higher than 100 µM for HUVEC, HCC1428 and T-47D cells. The sub-cytotoxic concentrations such as 25 µM, 50 µM and 100 µM were applied to determine anti-angiogenic and anti-migratory activities. Although the sub-cytotoxic concentrations inhibited endothelial tube formation and cellular migration in a concentration depended manner, barbatolic acid was more effective on the migration of HCC1428 and T-47D breast cancer cells than the migration of HUVECs. Consequently, the findings suggest that barbatolic acid is a promising anti-angiogenic and anti-migratory agent and the underlying activity mechanisms should be investigated by further in vitro and in vivo experiments. 相似文献
11.
Yunyun Wang Wen Gu Yu Shan Fei Liu Xu Xu Yiqin Yang Qiangjian Zhang Yan Zhang Hongbo Kuang Zhonglong Wang Shifa Wang 《Bioorganic & medicinal chemistry letters》2017,27(11):2360-2363
A series of new nopinone-based thiosemicarbazone derivatives were designed and synthesized as potent anticancer agents. All these compounds were identified by 1H NMR, 13C NMR, HR-MS spectra analyses. In the in vitro anticancer activity, most derivatives showed considerable cytotoxic activity against three human cancer cell lines (MDA-MB-231, SMMC-7721 and Hela). Among them, compound 4i exhibited most potent antitumor activity against three cancer cell lines with the IC50 values of 2.79 ± 0.38, 2.64 ± 0.17 and 3.64 ± 0.13 μM, respectively. Furthermore, the cell cycle analysis indicated that compound 4i caused cell cycle arrest of MDA-MB-231 cells at G2/M phase. The Annexin V-FITC/7-AAD dual staining assay also revealed that compound 4i induced the early apoptosis of MDA-MB-231 cells. 相似文献
12.
Wen Gu Ting-Ting Miao Da-Wei Hua Xiao-Yan Jin Xu-Bing Tao Chao-Bo Huang Shi-Fa Wang 《Bioorganic & medicinal chemistry letters》2017,27(5):1296-1300
A series of new 1H-benzo[d]imidazole derivatives of dehydroabietic acid were designed and synthesized as potent antitumor agents. Structures of the target molecules were characterized using MS, IR, 1H NMR, 13C NMR and elemental analyses. In the in vitro cytotoxic assay, most compounds showed significant cytotoxic activities against two hepatocarcinoma cells (SMMC-7721 and HepG2) and reduced cytotoxicity against noncancerous human hepatocyte (LO2). Among them, compound 7b exhibited the best cytotoxicity against SMMC-7721 cells (IC50: 0.36 ± 0.13 μM), while 7e was most potent to HepG2 cells (IC50: 0.12 ± 0.03 μM). The cell cycle analysis indicated that compound 7b caused cell cycle arrest of SMMC-7721 cells at G2/M phase. Further, compound 7b also induced the apoptosis of SMMC-7721 cells in Annexin V-APC/7-AAD binding assay. 相似文献
13.
Hua Sun Weina Ding Xiaotong Song Dong Wang Mingzhu Chen Kaili Wang Yazhou Zhang Peng Yuan Ying Ma Runling Wang Robert H. Dodd Yongmin Zhang Kui Lu Peng Yu 《Bioorganic & medicinal chemistry letters》2017,27(15):3226-3230
A series of 6-hydroxyaurones and their analogues have been synthesized and evaluated for their in vitro α-glucosidase inhibitory and glucose consumption-promoting activity. These compounds exhibited varying degrees of α-glucosidase inhibitory activity, 11 of them showing higher potency than that of the control standard acarbose (IC50 = 50.30 μM). Surprisingly, analogues devoid of a substituent at C-2 but having an aryl group at C-5 were found to be highly active (e.g., 7f, IC50 = 9.88 μM). Docking analysis substantiated these findings. The kinetic analysis of compound 7f, the most potent α-glucosidase inhibitor of this study, revealed that it inhibited α-glucosidase in an irreversible and mixed competitive mode. In addition, compounds 7f and 10c exhibited significant glucose consumption promoting activity at 1 μM. 相似文献
14.
Wenlin Xie Huilin Zhang Jingjing He Jingai Zhang Qiuyan Yu Chunxiang Luo Shangru Li 《Bioorganic & medicinal chemistry letters》2017,27(3):530-532
Two series of novel kojic acid analogues (4a–j) and (5a–d) were designed and synthesized, and their mushroom tyrosinase inhibitory activities was evaluated. The result indicated that all the synthesized derivatives exhibited excellent tyrosinase inhibitory properties having IC50 values in the range of 1.35 ± 2.15–17.50 ± 2.75 μM, whereas standard inhibitor kojic acid have IC50 values 20.00 ± 1.08 μM. Specifically, 5-phenyl-3-[5-hydroxy-4-pyrone-2-yl-methylmercap-to]-4-(2,4-dihydroxyl-benzylamino)-1,2,4-triazole (4f) exhibited the most potent tyrosinase inhibitory activity with IC50 value of 1.35 ± 2.15 μM. The kinetic studies of the compound (4f) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure-activity relationship was discussed. 相似文献
15.
Guangcheng Wang Xin Li Jing Wang Zhenzhen Xie Luyao Li Ming Chen Shan Chen Yaping Peng 《Bioorganic & medicinal chemistry letters》2017,27(5):1115-1118
A novel series of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides 5a–5q have been synthesized and evaluated for their α-glucosidase inhibitory activity. All newly synthesized compounds exhibited potent α-glucosidase inhibitory activity in the range of IC50 = 12.46 ± 0.13–72.68 ± 0.20 μM, when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Among the series, compound 5j (12.46 ± 0.13 μM) with strong electron-withdrawing nitro group on the arylacetamide moiety was identified as the most potent inhibitor of α-glucosidase. Molecular docking study was carried out to explore the binding interactions of these compounds with α-glucosidase. Our study identifies a novel series of potent α-glucosidase inhibitors for further investigation. 相似文献
16.
Ping Zhou Linsheng Huang Jie Zhou Bin Jiang Yanmei Zhao Xuehua Deng Qin Zhao Fei Li 《Bioorganic & medicinal chemistry letters》2017,27(17):4185-4189
A series of novel 4(1H)-quinolone derivatives was synthesized and evaluated for antiproliferative activity in vitro. The results showed that these compounds exhibited more potent antiproliferative effect against a panel of human tumor cell lines than the lead compound 7-chloro-4(1H)-quinolone 1. Compound 7e was found to be the most potent antiproliferative agent and to exhibit selective cytotoxic activity against HepG2 cell lines with IC50 value lower than 1.0 μM. Annexin V/FITC-PI assay showed that compound 7e induced apoptosis in HepG2 cells with a dose-dependent manner. Western blotting analysis indicated that compound 7e induced cell cycle arrest in G2/M phase by p53-depedent pathway. 相似文献
17.
Yichao Wan Tingting Liu Xiaoxian Li Chen Chen Hao Fang 《Bioorganic & medicinal chemistry》2017,25(1):138-152
As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki = 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki = 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki = 8.45 μM), which was the same as positive control Gossypol (Ki = 7.54 μM). 相似文献
18.
M. De Giorgi I. Pelikant-Malecka A. Sielicka E. M. Slominska R. Giovannoni A. Cinti 《Nucleosides, nucleotides & nucleic acids》2014,33(4-6):313-318
Adenine nucleosides and nucleotides are important signaling molecules involved in control of key mechanisms of xenotransplant rejection. Extracellular pathway that converts ATP and ADP to AMP, and AMP to adenosine mainly mediated by ecto-nucleoside triphosphate diphosphohydrolase 1, (ENTPD1 or CD39) and ecto-5′-nucleotidase (E5NT or CD73) respectively, is considered as important target for xenograft protection. To clarify feasibility of combined expression of human ENTPD1 and E5NT and to study its functional effect we transfected pig endothelial cell line (PIEC) with both genes together. To do this we have produced a dicistronic construct bearing F2A sequence in frame between human E5NT and human ENTPD1 coding sequences. PIEC cells were mock-transfected as transfection control or transfected with plasmids encoding human ENTPD1 or human E5NT. PIEC cells were exposed to 50 μM ATP or 50 μM ADP or 50 μM AMP. Conversion of extracellular substrates into products (ATP/ADP/AMP/adenosine) was measured by HPLC in the media collected at specific time intervals. Following addition of AMP, production of adenosine in the medium of E5NT/ENTPD1- and E5NT- transfected cells increased to 14.2 ± 1.1 and 24.5 ± 3.4 μM respectively while it remained below 1 μM in controls and in ENTPD1-transfected cells. A marked increase of adenosine formation from ADP or ATP was observed only in E5NT/ENTPD1-transfected cells (11.7 ± 0.1 and 5.7 ± 2.2 μM respectively) but not in any other condition studied. This study indicates feasibility and functionality of combined expression of human E5NT and ENTPD1 in pig endothelial cells using F2A sequence bearing construct. 相似文献
19.
Dechao Li Haizheng Liu Yufa Liu Qikun Zhang Chao Liu Shuhua Zhao Bo Jiao 《Bioorganic & medicinal chemistry letters》2017,27(3):533-536
The isolation and modification of natural products is always a very important resources to anti-tumor drugs. Therefore, a novel series of tetrandrine and fangchinoline derivatives were designed and synthesized, and their antiproliferative activities against HepG2, MCF-7 cells were evaluated and described. From the activity result obtained, high to very high activity in vitro has been found, one of the tested compounds (compound 5d) exhibited the most significant cytotoxic effects. Compound 5d increased 29.2, 7.37 times anti-proliferative activity for HepG2 cells and MCF-7 cells compared to sunitinib (IC50 = 16.06 μM and 25.41 μM). Finally flow cytometry determined that compound 5d could indeed inhibit the proliferation of HepG2 cells via inducing apoptosis. 相似文献
20.
Mary K. Yates Mithun R. Raje Payel Chatterjee Christina F. Spiropoulou Sina Bavari Mike Flint Veronica Soloveva Katherine L. Seley-Radtke 《Bioorganic & medicinal chemistry letters》2017,27(12):2800-2802
Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent against recombinant Ebola virus in Huh7 cells with an EC50 = 2 μM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC50 of 7 μM. 相似文献