- Design, synthesis of novel celastrol derivatives and study on their antitumor growth through HIF-1α pathway
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Four series of hypoxia-inducible factor-1 alpha (HIF-1α) functioning derivatives stemming from modifications to the C-29 carboxyl group of celastrol were designed and synthesized, and their anticancer activities were evaluated. To address the structure and activity relationship of each derivative, extensive structural changes were made. HRE luciferase reporter assay demonstrated that 12 modified compounds showed superior HIF-1α inhibitory activity. Among them, compound C6 exhibited the best features: firstly, the strongest HIF-1α inhibitory activity (IC50 = 0.05 μM, 5-fold higher than that of celastrol); secondly, lower cytotoxicity (22-fold lower, C6-16.85 μM vs celastrol-0.76 μM). Thus, the safety factor of C6 was about 112 times higher than that of celastrol. Western blot assay indicated that C6 may inhibit the expression of HIF-1α protein in cells. Additionally, C6 hindered tumor cell cloning, migration and induced cell apoptosis. It is worth mentioning that in the mouse tumor xenograft model, C6 (10 mg/kg) displayed good antitumor activity in vivo, showing a better inhibition rate (74.03%) than the reference compound 5-fluorouracil (inhibition rate, 59.58%). However, the celastrol treatment group experienced collective death after four doses of the drug. Moreover, C6 minimally affected the mouse weight, indicating that its application in vivo has little toxic effect. H&E staining experiments show that it could also exacerbate the degree of tumor cell damage. The results of water solubility experiment show that the solubility of C6 is increased by 1.36 times than that of celastrol. In conclusion, C6 is a promising antitumor agent through HIF-1α pathway.
- Shang, Fan-Fan,Wang, Jing Ying,Xu, Qian,Deng, Hao,Guo, Hong-Yan,Jin, Xuejun,Li, Xiaoting,Shen, Qing-Kun,Quan, Zhe-Shan
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- Design, Synthesis, and in Vitro and in Vivo Biological Evaluation of Limonin Derivatives for Anti-Inflammation Therapy
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In this study, limonin derivatives were used to design new anti-inflammatory compounds with high pharmacological activity and low toxicity. A total of 23 new limonin derivatives were discovered, synthesized, and screened for their anti-inflammatory activity against lipopolysaccharide (LPS)-treated RAW 264.7 cells. Of them, compound f4 was found to be the most active, with a higher efficiency compared with limonin and celecoxib. Subsequently, we studied the mechanism underlying the activity of f4 and found that it inhibited proinflammatory cytokines by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells as well as mice. In conclusion, f4 may be a promising anti-inflammatory lead compound.
- Bian, Ming,Gong, Guohua,Lei, Pang,Du, Huanhuan,Bai, Chunmei,Wei, Chengxi,Quan, Zheshan,Ma, Qianqian
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p. 13487 - 13499
(2021/11/17)
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- Design and synthesis of C-19 isosteviol derivatives as potent and highly selective antiproliferative agents
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Six series of novel isosteviol derivatives; modified in the C-19 position; were synthesized; and their antiproliferative activity was evaluated against three human cancer cell lines (HCT-116; BEL-7402; HepG2) and the human L02 normal cell line in vitro. M
- Luan, Tian,Cao, Li-Hua,Deng, Hao,Shen, Qing-Kun,Tian, Yu-Shun,Quan, Zhe-Shan
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- Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti- Toxoplasma gondii Agents
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Six series of (+)-usnic acid derivatives were synthesized. The IC50 values of these compounds were determined in T. gondii infected HeLa cells (μM) and in HeLa cells (μM), and their selectivity indexes (SI) were calculated. In vitro, most of th
- Guo, Hong-Yan,Jin, Chun-Mei,Jin, Chunmei,Quan, Zhe-Shan,Shen, Qing-Kun,Zhang, Hai-Ming
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- Synthesis and antitumor activities of novel rhein α-aminophosphonates conjugates
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Several rhein α-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited t
- Yao, Gui-Yang,Ye, Man-Yi,Huang, Ri-Zhen,Li, Ya-Jun,Pan, Ying-Ming,Xu, Qing,Liao, Zhi-Xin,Wang, Heng-Shan
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supporting information
p. 501 - 507
(2014/01/23)
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- Synthesis and antitumor activities of novel diacerein α-aminophosphonates conjugates
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Several diacerein α-aminophosphonates conjugates 4a-k have been synthesized, the structures of compounds have been characterized by IR, 1H NMR, 13C NMR, 31P NMR, ESI-MS spectra and elementary analysis. In vitro cytotoxicity against HepG-2, CNE, Spca-2 and Hct-116 cells are evaluated and employing standard MTT assay in comparing with commercial anticancer drug 5-fluorouracil (5-FU). Some compounds exhibit moderate to high levels of antitumor activity. Especially, compound 4i exhibit the strongest cytotoxicity against Hct-116 cells with IC50 9.83 μM. All the synthesized compounds exhibit low cytotoxicity against HUVEC cells. The mechanism of compound 4i has been preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicate that the compound 4i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis show that compound 4i mainly arrested Hct-116 cells in G1 stage. The effects of 4i on the activation of caspases expression indicate that 4i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 4i to DNA have been investigated by methods (UV-Vis, fluorescence, CD spectroscopy) in comparison with that of diacerein. Results indicate that 4i show moderate ability to interact ct-DNA.
- Qin, Jian-Mei,Li, Jian-Fei,Ye, Man-Yi,Huang, Ri-Zheng,Xu, Qing,Pan, Ying-Ming,Wang, Heng-Shan,Yao, Gui-Yang
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p. 1584 - 1595
(2015/02/02)
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- Synthesis and antitumor activities of novel α-aminophosphonates dehydroabietic acid derivatives
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A series of novel α-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma ce
- Huang, Xiao-Chao,Wang, Meng,Pan, Ying-Ming,Tian, Xiao-Yan,Wang, Heng-Shan,Zhang, Ye
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p. 5283 - 5289
(2013/09/23)
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- Synthesis and biological evaluation of novel phosphonates derivatives of as potential antitumor agents
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A series of dialkyl [2-(4,6-dimethoxypyrimidin-2-yloxy)benzamido](aryl) methylphosphonates derivatives were designed and synthesized. All the new compounds were identified by elemental analysis, IR, 1H NMR, 31P NMR, and MS. Their antitumor activity against KB and CNE1 cells was examined. Some of the compounds showed potential antitumor activity, which provided some hints for further study of structure modification. In particular, the compounds 6i and 6j displayed more potent cytotoxic activities against KB in comparison with 5-FU. Copyright Taylor & Francis Group, LLC.
- Jin, Chuanfei,Liang, Yong-Ju,He, Hongwu,Fu, Liwu
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p. 2096 - 2103
(2011/12/01)
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- Molecular iodine: An efficient catalyst for the one-pot synthesis of primary 1-aminophosphonates
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A new and convenient procedure has been developed for the one-pot synthesis of different types of primary 1-aminophosphonates from aldehydes/ketones, HMDS and diethyl phosphite using I2 as an inexpensive, non-toxic, non-metallic and readily available cata
- Sobhani,Vafaee
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experimental part
p. 227 - 236
(2010/10/21)
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- Solvent-and catalyst-free reaction of (aminomethyl)phosphonates with epoxides: Synthesis of novel {[(2-hydroxyethyl)amino]methyl}phosphonates
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Uncatalyzed reaction of epoxides with (aminomethyl)phosphonates for the synthesis of novel {[(2-hydroxyethyl)amino]methyl}phosphonates is described. Treatment of (aminomethyl)phosphonates with epoxides without any catalyst and under solvent-free condition
- Kaboudin, Babak,Sorbiun, Mina
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experimental part
p. 284 - 289
(2011/04/12)
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- Synthesis and herbicidal activity of O,O-diethyl N-{4-Methyl-[1,2,3] thiadiazole-5-carbonyl}- 1-amino-1-substitutedbenzyl phosphonates
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Target compounds 3 were synthesized by the condensation of O,O-diethyl α-amino substitutedbenzyl phosphonates 1 and 4-methyl-[1,2,3]thiadiazole- 5-carboxylic acid 2 in the presence of dicyclohexylcarbodiimide (DCC) as a dehydration reagent. Their structures were confirmed by spectroscopic data (IR, 1H NMR, 31P NMR, MS) and elemental analysis. The results of a preliminary bioassay (in vitro) indicated that some of the title compounds 3 possessed moderate to good herbicidal activities against dicotyledonous plants (Brassica campestris L) at the concentration of 100 mg/L, and most of these compounds exhibited higher herbicidal activities against dicotyledonous plants (Brassica campestris L) than monocotyledonous plants (Echinochloa crus-galli). Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Tang, Wu,Yu, Zhi-Hua,Shi, De-Qing
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scheme or table
p. 2024 - 2029
(2010/12/19)
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- Synthesis and herbicidal activity of novel pyrimidinyl derivatives containing an α-amino phosphonate moiety
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In order to find novel pyrimidinyl carboxylic acid analogs with high activity and low toxicity, a series of novel pyrimidinyl derivatives containing an -amino phosphonate moiety 5 was synthesized by the condensation of 4-(4,6-dimethoxypyrimidin-2-yloxy)phenoxyacetic 3a or propionic acids 3b with dialkyl -amino substitutedbenzyl phosphonates 4. Their structures were characterized by spectroscopic data (IR, 1H NMR, 31P NMR, MS) and elemental analyses. The results of preliminary herbicidal activities (in vitro) showed that most of these compounds exhibited higher herbicidal activities against dicotyledonous weeds (Brassica campestris L) than monocotyledonous weeds (Echinochloa crus-galli). Further bioassays (in vivo) indicated that some of compounds 5 possessed selective herbicidal activity against amaranth pigweed (A. retroflexus) in post-emergence treatment. Copyright Taylor & Francis Group, LLC.
- Yu, Zhi-Hua,Shi, De-Qing
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experimental part
p. 2316 - 2323
(2011/01/12)
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- Al(OTf)3 as an efficient catalyst for one-pot synthesis of primary diethyl 1-aminophosphonates under solvent-free conditions
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A simple and general method has been developed for the one-pot, three-component synthesis of a variety of primary 1-aminophosphonates catalyzed by Al(OTf)3 under solvent-free conditions in good to high yields. Copyright Taylor & Francis Group, LLC.
- Sobhani, Sara,Tashrifi, Zahra
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body text
p. 120 - 131
(2009/04/06)
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- One-pot synthesis of primary 1-aminophosphonates: Coupling reaction of carbonyl compounds, hexamethyldisilazane, and diethyl phosphite catalyzed by al(otf)3
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Al(OTf)3 has been utilized as a new and efficient catalyst for the selective synthesis of primary 1-aminophosphonates by a one-pot coupling reaction of various types of aldehydes/ketones, hexamethyldisilazane, and diethyl phosphite under solvent-free cond
- Sobhani, Sara,Tashrifi, Zahra
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experimental part
p. 109 - 115
(2009/09/29)
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- Silica-Supported Ammonium Hydrogen Carbonate as an Efficient Reagent for One-Pot Synthesis of 1-Aminophosphonates from Aldehydes
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Silica-supported ammonium hydrogen carbonate was found to be an efficient reagent for the synthesis of 1-aminophosphonates under microwave irradiation in solvent-free conditions. This method is an easy, rapid, one-pot, and good-yielding reaction for the s
- Kaboudin, Babak,Rahmani, Abbas
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p. 2705 - 2708
(2007/10/03)
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- A novel synthesis of diethyl 1-aminoarylmethylphosphonates on the surface of alumina
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A novel route has been devised for the preparation of a series of diethyl 1-aminoarylmethylphosphonates. The route involves facile reaction among aromatic aldehydes, diethyl hydrogen phosphite and HMDS on the surface of alumina.
- Sardarian,Kaboudin
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p. 2543 - 2546
(2007/10/03)
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- STUDIES ON ORGANOPHOSPHORUS COMPOUNDS. 65, A FACILE SYNTHETIC ROUTE TO PHOSPHONOPEPTIDES
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A direct procedure for the preparation of phosphonopeptides, containing either a N- or C-terminal phosphonic acid residue, is described.This method is based on a three component condensation reaction leading to diethyl 1-(N-carbobenzyloxyamino)-alkylphosp
- Yuan, Chengye,Wang, Guohong
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p. 207 - 212
(2007/10/02)
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- ORGANIC PHOSPHORUS COMPOUNDS 94 PREPARATION, PHYSICAL AND BIOLOGICAL PROPERTIES OF AMINO-ARYLMETHYLPHOSPHONIC- AND -PHOSPHONOUS ACIDS
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The preparation, physical and spectroscopic properties of amino-arylmethylphosphonic- and -phosphonous acids, the phosphorus analogues of phenylglycine, are described.It is shown that several of the compounds prepared exhibit antifungal activity at 200 ppm.Thus 1e, 1f, 1g and 1h showed activity against Erysiphe (barley), 2a against Puccinia (wheat) and 6a against Botrytis (apple).Of particular interest is the high gameticidal activity of 3a in the greenhouse.
- Maier, Ludwig,Diel, Peter J.
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