MOLECULES
·
2021
·Vol. 26
·期 5
·1380
·
IF 4.412
Xiutao Wu,Lijie Gong,Chen Chen,Ye Tao,Wuxi Zhou,Lingyi Kong,Jianguang Luo
Harringtonolide (HO), a natural product isolated fromCephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound6exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.Keywords:harringtonolide;troponoids;structure-activity relationship (SAR);antiproliferative activity
研究领域:
药物化学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2013
·Vol. 18
·期 5
·5420-5433
·
IF 2.428
Fan Chao,Dong-En Wang,Rui Liu,Qin Tu,Jian-Jun Liu,Jinyi Wang
A series of new matrinic acid derivatives5a–ewas synthesized. The chemical structures of the synthesized compounds were confirmed by1H-NMR,13C-NMR, and electrospray ionization mass spectroscopy. The anti-tumor activities were also investigatedin vitroby evaluating the effect of synthesized compounds on the proliferation of A375, A549, HeLa, and HepG2 cells. Compound5ewas found to be the most potent against A375 and HeLa cells, with IC50values of 37 and 75.5 μg/mL, respectively. Compounds5b,5c,5g, and5halso exhibited antiproliferative activities against A549 cells, with IC50values within the 36.2–47 μg/mL range. For HepG2 cells,5eand5i, with IC50values of 78.9 and 61 μg/mL, respectively, showed higher antiproliferative activity than taxol.Keywords:matrinic acid derivative;synthesis;antiproliferative activity
研究领域:
药物化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Yufeng Zou,Jianbo Zhang,Yumin Niu,Dengyong Liu
The key constituent(s) of sugar-smoking brown pigments were identified, the chemical and biological properties were subsequently investigated, and the possibility of obtaining it from nature was explored. A pigment was isolated, which was identified as condensation product of 5-hydroxymethyl-2-furfuraldehyde (5-HMF) with glucose: 5-(α-D-glucopyranosyl-(1–6)-α-D-glucopyranosyloxymenthyl)-2-furancarboxaldehyde (5-GGMF). The molecular weight was 450.00. The interaction between pigment with protein on chicken skin was mainly via hydrogen and carbon-hydrogen bonds. It was obtained by caramelization instead of Maillard reaction. Discoloration of sugar-smoking pigments were mainly due to cleavage of chromophores caused by the oxidation reaction followed by photobleaching mechanism. Both radical scavenging and antiproliferative capacity of sugar-smoking pigment were in a dose-dependent manner. However, the IC 50 values for HepG2 and PANC-1 cells differed by more than ten times. Since 5-GGMF is also present in plant resources (like Rehmanniae Radix ), it can be obtained as natural additive to produce clean label sugar-smoked meat products.
研究领域:
食品科学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
npj Breast Cancer
·
2024
·Vol. 10
·期 1
·1-15
·
IF 6.5
Rossetti Stefano,Broege Aaron,Sen Adrish,Khan Salmaan,MacNeil Ian,Molden Jhomary,Kopher Ross,Schulz Stephen,Laing Lance
The PI3K, AKT, and mTOR (PAM) pathway is frequently dysregulated in breast cancer (BC) to accommodate high catabolic and anabolic activities driving tumor growth. Current therapeutic options for patients with hormone receptor (HR) + / HER2- advanced BC (ABC) include PAM inhibitors that selectively inhibit only one PAM pathway node, which can lead to drug resistance as cells rapidly adapt to maintain viability. We hypothesized that gedatolisib, which potently inhibits all Class I PI3K isoforms, as well as mTORC1 and mTORC2, may be more effective in BC cells than single-node PAM inhibitors by limiting adaptive resistances. By using multiple functional assays, a panel of BC cell lines was evaluated for their sensitivity to four different PAM inhibitors: gedatolisib (pan-PI3K/mTOR inhibitor), alpelisib (PI3Kα inhibitor), capivasertib (AKT inhibitor), and everolimus (mTORC1 inhibitor). Gedatolisib exhibited more potent and efficacious anti-proliferative and cytotoxic effects regardless of the PAM pathway mutational status of the cell lines compared to the single-node PAM inhibitors. The higher efficacy of gedatolisib was confirmed in three-dimensional culture and in BC PDX models. Mechanistically, gedatolisib decreased cell survival, DNA replication, cell migration and invasion, protein synthesis, glucose consumption, lactate production, and oxygen consumption more effectively than the other PAM inhibitors tested. These results indicate that inhibition of multiple PAM pathway nodes by a pan-PI3K/mTOR inhibitor like gedatolisib may be more effective at inducing anti-tumor activity than single-node PAM inhibitors. A global Phase 3 study is currently evaluating gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/HER2− ABC.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Hui Xu,Ye Hu,Qiuhui Hu,Jianhui Liu,Anxiang Su,Minhao Xie,Gaoxing Ma,Fei Pei,Alfred Mugambi Mariga,Wenjian Yang
Flammulina velutipes has anti-inflammatory, immunomodulatory, antioxidant and many bioactive properties with high contents of carbohydrate, proteins and fibers. In this study, a novel proteoglycan with polysaccharide complexes and protein chain, named PGD1-1, was isolated from F. velutipes . The structural characteristics of PGD1-1 were then determined, and its anti-proliferation and pro-apoptotic activities against HepG-2 cells were demonstrated in vitro. Results proved that the average molecular weight of PGD1-1 was 32.71 kDa, and the carbohydrate and protein contents were 93.35 and 2.33%, respectively. The protein moiety was bonded to a polysaccharide chain via O-glycosidic linkage. The monosaccharides consisted of d -glucose, D-galactose and D-xylose in a molar ratio of 21.90:2.84:1.00. PGD1-1 significantly inhibited the proliferation of HepG-2 cells by affecting cell lipid peroxidation and nitric oxide production. In addition, PGD1-1 promoted the apoptosis of HepG-2 cells, especially the early apoptosis. These findings proved that PGD1-1 was a novel potent ingredient against the proliferation of HepG-2, which will provide a theoretical basis for the development and utilization of the functional ingredients of the F. velutipes .
研究领域:
分子生物学
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肿瘤学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
eFood
·
2022
·Vol. 3
·期 3
·e13
·
IF 0
Hui Cao,Petra Högger,Miguel-Angel Prieto,Jesus Simal-Gandara,Jianbo Xiao
Quercetin is evidently unstable in Dulbecco's modified Eagle's medium (DMEM) at 37°C. However, the underlying mechanism of this instability is not clear yet. The stability and new degradation products of quercetin in DMEM at 37°C were investigated via in UPLC-MS-MS analysis. With increasing incubation time, quercetin formed various degradation products derived from its dimer and there were numerous isomers formed during this process. Ascorbic acid significantly improved the stability of quercetin by protecting quercetin from auto-oxidation in this medium. Ascorbic acid also remarkably enhanced the stability of quercetin in DMEM in the presence of A549 cells and obviously increased the antiproliferative effect of quercetin toward A549 cells.
研究领域:
药理学
·
细胞生物学
✓ 已验证
DOI
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2021
·
IF 3.77
O.Yu. Selyutina,P.A. Kononova,V.E. Koshman,E.A. Shelepova,M. Gholam Azad,R. Afroz,M. Dharmasivam,Paul V. Bernhardt,N.E. Polyakov,D.R. Richardson
Background Iron (Fe)-induced oxidative stress leads to reactive oxygen species that damage biomembranes, with this mechanism being involved in the activity of some anti-cancer chemotherapeutics. Methods Herein, we compared the effect of the ligand, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), or the potential ligand, Emodin, on Fe-catalyzed lipid peroxidation in cell membrane models (micelles and bicelles). These studies were performed in the presence of hydrogen peroxide (H 2 O 2 ) and the absence or presence of ascorbate. Results In the absence of ascorbate, Fe(II)/Emodin mixtures incubated with H 2 O 2 demonstrated slight pro-oxidant properties on micelles versus Fe(II) alone, while the Fe(III)-Dp44mT complex exhibited marked antioxidant properties. Examining more physiologically relevant phospholipid-containing bicelles, the Fe(II)- and Fe(III)-Dp44mT complexes demonstrated antioxidant activity without ascorbate. Upon adding ascorbate, there was a significant increase in the peroxidation of micelles and bicelles in the presence of unchelated Fe(II) and H 2 O 2 . The addition of ascorbate to Fe(III)-Dp44mT substantially increased the peroxidation of micelles and bicelles, with the Fe(III)-Dp44mT complex being reduced by ascorbate to the Fe(II) state, explaining the increased reactivity. Electron paramagnetic resonance spectroscopy demonstrated ascorbyl radical anion generation after mixing ascorbate and Emodin, with signal intensity being enhanced by H 2 O 2 . This finding suggested Emodin semiquinone radical formation that could play a role in its reactivity via ascorbate-driven redox cycling. Examining cultured melanoma cells in vitro , ascorbate at pharmacological levels enhanced the anti-proliferative activity of Dp44mT and Emodin. Conclusions and general significance Ascorbate-driven redox cycling of Dp44mT and Emodin promotes their anti-proliferative activity.
研究领域:
生物化学
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药理学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2019
·Vol. 28
·期 6
·892-899
·
IF 1.72
Sun Li,Chu Xiang-Wu,Liu Chun-mei,Sheng Li-Xin,Chen Zhuan-Xin,Cheng Ke-Guang
As pharmacophore hybridization has been used frequently in the discovery of new drugs, ursolic acid/glycyrrhetinic acid-uracil/thymine hybrids have been synthesized and evaluated their antiproliferative activity by the MTT assay. The results displayed that, the hybrids of glycyrrhetinic acid ( 7a – 7b to 10a – 10b ) exhibited slightly better antiproliferative activity than that of ursolic acid hybrids ( 3a – 3b to 6a – 6b ). Two single glycyrrhetinic acid-thymine hybrids ( 8a and 10a ) possessed good antiproliferative activity against tested A549 cell line (IC 50 = 10.7 and 18.3 µM, respectively). And three hybrids ( 3a , 5a , and 10b ) exhibited about 80% inhibitory ratio against tested Hela cell line.
研究领域:
药物化学
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肿瘤学
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分子生物学
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药理学
✓ 已验证
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Xue Bai,Yinuo Liu,Yuchen Cao,Zhouye Ma,Yue Chen,Shuai Guo
Background Lung cancer is a highly malignant disease with limited treatment options and significant adverse effects . It is urgent to develop novel treatment strategies for lung cancer. In recent years, TMEM16A has been confirmed as a specific drug target for lung cancer. The development of TMEM16A-targeting drugs and combined administration for the treatment of lung cancer has become a research hotspot. Methods Fluorescence screening and electrophysiological experiments were conducted to confirm the inhibitory effect of CCA on TMEM16A. Molecular dynamics simulation and site-directed mutagenesis were employed to analyze the binding mode of CCA and TMEM16A. CCK-8, colony formation, wound healing , transwell, and annexin-V experiments were conducted to explore the regulatory effects and mechanisms of CCA on the proliferation, migration, and apoptosis of lung cancer cells. Tumor model mice and pharmacokinetic experiments were used to examine the efficacy and safety of CCA and cisplatin in vivo . Results This study firstly confirmed that CCA effectively inhibits TMEM16A to exert anticancer effects and analyzed the pharmacological mechanism. CCA bound to S517/N546/E623/E633/Q637 of TMEM16A through hydrogen bonding and electrostatic interactions. It inhibited the proliferation and migration, and induced apoptosis of lung cancer cells by targeting TMEM16A. In addition, the combined administration of CCA and cisplatin exhibited a synergistic effect, enhancing the efficacy of lung cancer treatment while reducing side effects . Conclusion CCA is an effective novel inhibitor of TMEM16A, and it synergizes with cisplatin in anticancer treatment. These findings will provide new research ideas and lead compound for the combination therapy of lung cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2020
·
IF 2.69
Shiya Zhou,Shuwen Fu,Hanle Wang,Yanhao Deng,Xing Zhou,Wei Sun,Yinglei Zhai
Acidic tumor microenvironment has been extensively explored to design pH-responsive paclitaxel prodrug micelles for cancer therapy. The object of this study is to investigate the pH-responsive drug release behavior and the anti-proliferation capacity of acetal-linked paclitaxel polymeric prodrug micelles. The prodrug was synthesized and evaluated for paclitaxel content. The prodrug micelles were fabricated and characterized for morphology, size, in vitro pH-responsive paclitaxel release, cellular uptake, and anti-proliferation. Paclitaxel content was 33 wt%. The prodrug micelles exhibited spherical structure with the hydrodynamic diameter of 154 nm. Besides, the in vitro paclitaxel release behavior was verified to be pH-responsive, and 77%, 38%, and 17% of parent free paclitaxel was released from the nano-sized prodrug micelles in 13 h at pH 5.5, 6.5, and 7.4, respectively. The cellular uptake assessment demonstrated the time-dependent internalization of prodrug micelles. Meanwhile, CCK-8 analysis showed that prodrug micelles possessed the potent anti-proliferation effects. Prodrug micelles based on aliphatic polycarbonates present a promising platform for cancer chemotherapy due to the pH-responsive characteristics of acetal bond, potent anti-proliferation effects, and outstanding cytocompatibility of aliphatic polycarbonates.
研究领域:
药物递送
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2016
·
IF 4.219
Chao Li,Xiangshi Li,Lijun You,Xiong Fu,Rui Hai Liu
Sargassum pallidum polysaccharides were fractioned using a DEAE-Sepharose fast-flow column and four polysaccharide fractions (SP-P1, SP-P2, PV-P3 and SP-P4) were obtained. Structural analyses indicated that SP-P2 and SP-P4 had higher molecular weights than SP-P1 and SP-P3. SP-P2, SP-P3 and SP-P4 comprised of fucose, rhamnose, arabinose, galactose, glucose, xylose, and mannose in a similar molar ratio, while SP-P1 did not contain arabinose. SP-P2 and SP-P4 had a similar number of (1 → 6) or (1→) glycosidic linkages (1 → 2) or (1 → 4) glycosidic linkages and (1 → 3) glycosidic linkages, while SP-P1 and SP-P3 contained a small number of (1 → 3) glycosidic linkages. SP-P2 exhibited better bioactivities than SP-P1, SP-P3 and SP-P4, including antioxidant, anti-hemolysis inhibitory, α-amylase and α-glucosidase inhibitory and antiproliferative activities. These data suggest that S. pallidum has four polysaccharide fractions with different structural features and bioactivities and SP-P2 has potential to be explored as a functional food or complementary medicine.
研究领域:
海洋生物学
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食品科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF PHARMACAL RESEARCH
·
2016
·Vol. 39
·期 7
·871-877
·
IF 2.49
Li Da-hong,Guo Jia,Bin Wen,Zhao Nan,Wang Kai-bo,Li Jian-yong,Li Zhan-lin,Hua Hui-ming
Two novel rare chloro-containing benzylisoquinoline alkaloids, thalfoliolosumines A ( 1 ) and B ( 2 ), along with eight known isoquinoline alkaloids ( 3 – 10 ) were isolated from the whole plant of Thalictrum foliolosum . The structures of these compounds were elucidated by spectral analyses, including 1D and 2D NMR (COSY, HSQC, HMBC and NOESY) experiments. The antiproliferative effects of all the isolated compounds were evaluated by MTT method against MCF-7, PC-3, and U937 cells, and trypan blue method against HL-60 cells. New compounds 1 and 2 exhibited moderate in vitro antiproliferative activity against MCF-7, PC-3, and HL-60 cells, and good inhibitory effects against U937 cells with IC 50 values of 7.50 and 6.97 μM, respectively. Compounds 7 and 10 showed the strongest in vitro antiproliferative with IC 50 values of 0.93 and 1.69 μM against HL-60 cell line. The antioxidant properties were also measured, bisbenzyltetrahydroisoquinoline alkaloids 3 – 6 showed the strongest antioxidant activities in ABTS assay.
研究领域:
药理学
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植物化学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）