- Development of coumarin-based hydroxamates as histone deacetylase inhibitors with antitumor activities
-
Histone deacetylases (HDACs) have been proved to be promising targets for the treatment of cancer, and five histone deacetylase inhibitors (HDACis) have been approved on the market for the treatment of different lymphomas. In our previous work, we designed a series of novel coumarin-containing hydroxamate HDACis, among which compounds 6 and 7 displayed promising activities against tumor growth. Based on a molecular docking study, we further developed 26 additional analogues with the aim to improve activity of designed compounds. Several of these new derivatives not only showed excellent HDAC1 inhibitory effects, but also displayed significant growth inhibitory activities against four human cancer cell lines. Representative compounds, 13a and 13c, showed potent anti-proliferative activities against solid tumor cell lines with IC50 values of 0.36–2.91 μM and low cytotoxicity against Beas-2B and L-02 normal cells. Immunoblot analysis revealed that 13a and 13c dose-dependently increased the acetylation of histone H3 and H4. Importantly, the two compounds displayed much better anti-metastatic effects than SAHA against the MDA-MB-231 cell line. Moreover, 13a and 13c arrested MDA-MB-231 cells at G2/M phase and induced MDA-MB-231 cell apoptosis. Finally, the molecular docking study rationalized the high potency of compound 13c.
- Zhao, Na,Yang, Feifei,Han, Lina,Qu, Yuhua,Ge, Di,Zhang, Hua
-
-
Read Online
- Microwave-promoted Synthesis of Novel Fused Osthole Analogues
-
Osthole is a natural coumarin derivative and has a broad scope of biological activities. Two series of novel fused osthole analogues were designed, and synthesized through a highly efficient microwave-promoted synthetic protocol via the reaction of 4-hydroxycoumarins and β-ketoesters. The reaction conditions including solvent, catalyst, microwave power and irradiation time were also optimized. The pyrano[3,2-c]chromene-2,5-diones and furo[3,2-c]coumarins were obtained through two distinct intramolecular cyclization processes, and the proposed mechanism was also discussed.
- Zhang, Mingzhi,Zhang, Rongrong,Wang, Jiaqun,Yu, Xiang,Zhang, Yaling,Wang, Qingqing,Zhang, Weihua
-
-
Read Online
- Thienochromene derivatives inhibit pSTAT1 and pSTAT5 signaling induced by cytokines
-
Furanocoumarins, particularly furo[3,2-c]coumarins, are found in many natural products. However, coumarins annulated to a thiophene ring have received scarce attention to date in the literature. Therefore, we synthesized 4-oxo-4H-thieno[3,2-c]chromene derivatives and tested in vitro their anti-inflammatory activity. Anti-inflammatory potential of the synthesized compounds (1, 2, 6–8, 9a–e and 10a–c) has been evaluated by measuring various pSTAT (signal transducer and activator of transcription) inhibition within the JAK (Janus-activated family kinase)/STAT signaling pathway. Ethyl 7-hydroxy-4-oxo-4H-thieno[3,2-c]chromene-2-carboxylate (7) showed best inhibition properties on pSTAT5 in GM-CSF (Granulocyte-macrophage colony-stimulating factor)-triggered PBMC assay, with IC50 value of 5.0 μM.
- Andjelkovic, Uro?,Antolovi?, Roberto,Bracanovi?, Sara,Cetina, Mario,Jeli?, Dubravko,Kraljevi? Paveli?, Sandra,Vinter, Adrijana,Wittine, Karlo,Wittine, Ozren
-
-
Read Online
- Synthesis and discovery of new compounds bearing coumarin scaffold for the treatment of pulmonary fibrosis
-
Idiopathic pulmonary fibrosis, characterized by excess accumulation of extracellular matrix, involved in many chronic diseases or injuries, threatens human health greatly. We have reported a series of compounds bearing coumarin scaffold which potently inhibited TGF-β-induced total collagen accumulation in NRK-49F cell line and migration of macrophages. Compound 9d also suppressed the TGF-β-induced protein expression of COL1A1, α-SMA, and p-Smad3 in vitro. Meanwhile, 9d at a dose of 100 mg/kg/day through oral administrations for 4 weeks effectively alleviated infiltration of inflammatory cells in lung tissue and fibrotic degree in bleomycin-induced pulmonary fibrosis model, which may related to its inhibition of TGF-β/Smad3 pathway and anti-inflammation efficacy. In addition, 9d demonstrated decent bioavailability (F = 39.88%) and suitable eliminated half-life time (T1/2 = 13.09 h), suggesting that 9d could be a potential drug candidate for the treatment of fibrotic diseases.
- Deng, Dexin,Pei, Heying,Lan, Tingxuan,Zhu, Jiali,Tang, Minghai,Xue, Linlin,Yang, Zhuang,Zheng, Shoujun,Ye, Haoyu,Chen, Lijuan
-
-
Read Online
- Ferulin C triggers potent PAK1 and p21-mediated anti-tumor effects in breast cancer by inhibiting Tubulin polymerization in vitro and in vivo
-
Ferulin C, a natural sesquiterpene coumarin, isolated from the roots of Ferula ferulaeoides (Steud.) Korov, displaying potent antiproliferatory activity against breast cancer cells. This study aimed to elucidate the underlying molecular mechanisms of Ferulin C-induced breast cancer cells death in vitro and in vivo. Ferulin C presented potent antiproliferatory activity against MCF-7 and MDA-MB-231 cells and remarkable tubulin polymerization inhibitory activity (IC50 = 9.2 μM). Meanwhile, we predicted Ferulin C bind to the Colchicine site of tubulin through CETSA assay, molecular docking and molecular dynamics (MD) simulations. In immunofluorescence assay, Ferulin C disturbed the microtubule integrity and structure. Furthermore, Ferulin C stimulated significant cell cycle arrest in the G1/S period via p21Cip1/Waf1 - CDK2 signaling, induced classic cell apoptosis, impaired metastasis via down-regulating Ras-Raf-ERK and AKT-mTOR signaling. Intriguingly, Ferulin C treatment induced autophagy by ULK1 signaling to synergize with the inhibition of proliferation and metastasis. Based upon the RNAseq analysis, PAK1, as a novel essential modulator, was involved in the signaling regulated by Ferulin C -induced α/β-tubulin depolymerization. Additionally, Ferulin C displayed an acceptable antiproliferatory activity in an MCF-7 xenograft model without inducing obvious weight loss in the Ferulin C treated mice. Summarily, our findings substantiated that Ferulin C was a potent, colchicine site binding microtubule-destabilizing agent with anti-proliferation and anti-metastasis activity via PAK1 and p21-mediated signaling in breast cancer cells.
- He, Zhendan,Huang, Jian,Pan, Dabo,Wang, Jinhui,Yao, Dahong,Zhang, Jin,Zhen, Yongqi
-
-
Read Online
- Coumarin derivative and analogue, preparation method and application thereof
-
The invention relates to a coumarin derivative and analogue, a preparation method and application thereof, belongs to the field of chemical medicines, and provides a compound shown as a formula I or apharmaceutically acceptable salt thereof, and a preparation method and application of the compound. According to the invention, biological experiments show that the compound has a strong in-vitro anti-fibrosis effect, can obviously reduce deposition of intercellular collagenous fibers on TGF-beta induced NRK-49F cells, and has inhibition on migration of HUVEC cells; and the compound with the structure has a certain curative effect on carbon tetrachloride induced hepatic fibrosis and bleomycin induced pulmonary fibrosis mouse models, is relatively low in toxicity, and provides a new choice forclinical treatment of tissue fibrosis diseases including hepatic fibrosis, pulmonary fibrosis and renal fibrosis.
- -
-
Paragraph 0179-0182
(2021/03/31)
-
- Copper(II)-Catalyzed Tandem Reaction: Synthesis of Furo[3,2- c]coumarin Derivatives and Evaluation for Photophysical Properties
-
An efficient protocol for synthesizing furo[3,2-c]coumarin derivatives is described. The novel reaction could afford the desired furocoumarins with good to excellent yields in a mild and rapid manner. Large substrate scope screening and scale-up preparation have also been accomplished, and selected compounds were evaluated for their photophysical properties.
- Feng, Xi,Qin, Zhen,Cheng, Xinying,Liu, Dongyu,Peng, Yinghe,Huang, Huidan,Song, Bin,Bian, Jinlei,Li, Zhiyu
-
supporting information
p. 12537 - 12548
(2021/09/20)
-
- Discovery of N-(4-(3-isopropyl-2-methyl-2 H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies
-
Hematologic malignancies (HM) start in blood forming tissue or in the cells of the immune system. Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and some of them control cellular transcription. CDK inhibition can trigger apoptosis and could be particularly useful in hematological malignancies. Herein, we describe our efforts toward the discovery of a novel series of quinazoline derivatives as CDK inhibitors. Intensive structural modifications lead to the identification of compound 37d as the most active inhibitors of CDKs 1, 2, 4, 8 and 9 with balancing potency and selectivity against CDKs. Further biological studies revealed that compound 37d can arrest the cell cycle and induce apoptosis via activating PARP and caspase 3. More importantly, compound 37d showed good antitumor efficacy in multiple HM mice xenograft models with no obvious toxicity. These results indicated that CDK 1, 2, 4, 8, and 9 inhibitors could be potentially used to treat certain hematologic malignancies.
- Huang, Jianhang,Wang, Xinren,Dong, Ruinan,Liu, Xiaoyue,Li, Hongmei,Zhang, Tianyi,Xu, Junyu,Liu, Chenhe,Zhang, Yanmin,Hou, Shaohua,Tang, Weifang,Lu, Tao,Chen, Yadong
-
supporting information
p. 12548 - 12571
(2021/09/11)
-
- Preparation method and application of N-(pyrimidine-2-yl) coumarin-7-amine derivative as protein kinase inhibitor
-
The invention discloses a cyclin-dependent kinase inhibitor. The cyclin-dependent kinase inhibitor comprises an N-(pyrimidine-2-yl) coumarin-7-amine derivative shown as a general formula (I). In-vitropharmacodynamic tests prove that the compound has a high-selectivity inhibition effect on CDK9 kinase, and can be applied to reducing or inhibiting the activity of CDK9 kinase in cells. The inventionalso discloses a preparation method of the inhibitor and application of the inhibitor in drugs for CDK family kinase mediated diseases, especially hyperproliferative diseases, virus-induced infectious diseases and cardiovascular diseases.
- -
-
Paragraph 0283; 0286-0288
(2020/12/14)
-
- Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity
-
Specific inhibition of CDK9 is considered a promising strategy for developing effective anticancer therapeutics. However, most of the reported CDK9 inhibitors are still at an early stage of development and lack selectivity against other CDKs. Herein, we discovered coumarin derivative 30i as a potent CDK9 inhibitor with high selectivity (8300-fold over CDK7). Binding mode analysis illustrated that the substituent coumarin moiety is a critical group for CDK9 selectivity by occupying a flexible hinge/αD region, which is sterically hindered in other CDKs. Compound 30i showed excellent cellular antiproliferative activity, moderate pharmacokinetic property and low hERG inhibition. Moreover, 30i significantly induced tumour growth inhibition in a dose-dependent manner without causing an obvious loss of body weight in an MV4-11 xenograft mice model. Altogether, these results suggest that 30i may serve as a potential acute myeloid leukaemia (AML) therapeutics by selectively targeting CDK9.
- Chen, Yadong,Dong, Ruinan,Duan, Chunqi,Huang, Jianhang,Jiang, Fei,Li, Hongmei,Li, Shuwen,Liu, Chenhe,Lu, Tao,Tang, Weifang,Wang, Xinren,Xu, Junyu,Zhang, Tianyi,Zhang, Yanmin,Zhu, Gaoyuan,Zhu, Yuqin
-
-
- Regioselective Synthesis of 4,5-Dihydro-6H-oxepino[3,2-c]chromene-2,6(3H)-diones through Palladium-Catalyzed Intramolecular Alkoxycarbonylation of 3-Allyl-4-hydroxycoumarins
-
Seven-membered ring lactones fused to coumarin scaffolds were obtained via a palladium-catalyzed regioselective intramolecular alkoxycarbonylation under a CO atmosphere. Cyclocarbonylation of 3-allyl-4-hydroxycoumarin derivatives was accessed in the absen
- Sosa, D. Oliver,Almaraz, Karla,Amézquita-Valencia, Manuel
-
supporting information
p. 4682 - 4687
(2019/08/01)
-
- Novel conjugates of podophyllotoxin and coumarin: Synthesis, cytotoxicities, cell cycle arrest, binding CT DNA and inhibition of Topo IIβ
-
A series of conjugates of podophyllotoxin and coumarin were prepared using the click reaction, and their cytotoxicities against A549, HepG2, HeLa, and LoVo cells were evaluated. Among them, compound 14e exhibited the strongest cytotoxicities against these cancer cells with IC50 values of 4.9–17.5 μM. Furthermore, 14e disrupted microtubules and induced cell cycle arrest at G1 phase by regulating P21 and Cyclin D1 in LoVo cells. In addition, 14e bond CT DNA and selectively inhibited Topo IIβ over Topo IIα. Molecular docking model showed that 14e appeared to form stable hydrogen bonds with several DNA bases and residue Gln778. Taken together, these conjugates have the potential to be developed as anti-tumor drugs.
- Hao, Shu-Yi,Feng, Shi-Liang,Wang, Xing-Rong,Wang, Zhichao,Chen, Shi-Wu,Hui, Ling
-
supporting information
p. 2129 - 2135
(2019/07/05)
-
- Design, synthesis and biological evaluation of novel coumarin-based hydroxamate derivatives as histone deacetylase (HDAC) inhibitors with antitumor activities
-
A series of novel coumarin-based hydroxamate derivatives were designed and synthesized as histone deacetylase inhibitors (HDACis). Selective compounds showed a potent HDAC inhibition with nM IC50 values, with the best compound (10e) being nearly 90 times more active than vorinostat (SAHA) against HDAC1. Compounds 10e and 11d also increased the levels of acetylated histone H3 and H4, which is consistent with their strong HDAC inhibition. In addition, 10e and 11d displayed a higher potency toward human A549 and Hela cancer cell lines compared with SAHA. Moreover, 10e and 11d significantly arrested A549 cells at the G2/M phase and enhanced apoptosis. Molecular docking studies revealed the possible mode of interaction of compounds 10e and 12a with HDAC1. Our findings suggest that these novel coumarin-based HDAC inhibitors provide a promising scaffold for the development of new potential cancer chemotherapies.
- Yang, Feifei,Zhao, Na,Song, Jiali,Zhu, Kongkai,Jiang, Cheng-shi,Shan, Peipei,Zhang, Hua
-
-
- One-pot two-step synthesis of 3-iodo-4-aryloxy coumarins and their Pd/C-catalyzed annulation to coumestans
-
An efficient protocol for the synthesis of various coumestans from the intramolecular annulation of 3-iodo-4-aryloxy coumarins through C-H activation has been developed. When 3-iodo-4-aryloxy coumarins were treated with 10% Pd/C (0.3 mol% Pd) in the presence of sodium acetate, the corresponding coumestans were produced in good to excellent yield. Reusability of the palladium catalyst was investigated in up to three consecutive cycles and it was found that the yield of the reaction was almost unaltered. Sequential iodination and O-arylation of 4-hydroxy coumarins leading to the 3-iodo-4-aryloxy coumarins were also achieved in a one-pot two-step process starting from aryl iodides in high yield. Pivalic acid was revealed to be the most effective additive for the later method to produce 3-iodo-4-phenoxy coumarins. Different functional groups bearing electron-donating as well as withdrawing groups are also tolerant to the reaction conditions.
- Panda, Niranjan,Mattan, Irshad
-
p. 7716 - 7725
(2018/03/01)
-
- Annulation of β-naphthols and 4-hydroxycoumarins with vinylsulfonium salts: Synthesis of dihydrofuran derivatives
-
A new synthetic approach to dihydrofuran derivatives via the annulation reaction of β-naphthols and 4-hydroxycoumarins with vinylsulfonium salts has been developed. A variety of dihydrofuran derivatives were prepared in moderate to good yields under mild conditions. The products could be readily transformed to the corresponding furans via the dehydrogenation with DDQ.
- Chen, Zi-Cong,Tong, Lang,Du, Zhi-Bo,Mao, Zhi-Feng,Zhang, Xue-Jing,Zou, Yong,Yan, Ming
-
supporting information
p. 2634 - 2638
(2018/04/26)
-
- Synthesis of furo[3,2-c]coumarins via I2/TBHP-mediated reaction of 4-hydroxycoumarins with terminal alkynes
-
An efficient I2/TBHP-mediated process for the formation of furo[3,2-c]coumarins from readily available materials has been developed. This process for the formation of furo[3,2-c]coumarins is quite environmental friendly and atom-economical.
- Chu, Xianglong,Tang, Ziqiang,Ma, Jiangshan,He, Libowen,Feng, Lei,Ma, Chen
-
p. 970 - 974
(2018/02/09)
-
- Dual functional small molecule fluorescent probes for image-guided estrogen receptor-specific targeting coupled potent antiproliferative potency for breast cancer therapy
-
A strategy by integrating biological imaging into early stages of the drug discovery process can improve our understanding of drug activity during preclinical and clinical study. In this article, we designed and synthesized coumarin-based nonsteroidal type fluorescence ligands for drug-target binding imaging. Among these synthesized compounds, 3e, 3f and 3h showed potent ER binding affinity and 3e (IC50?=?0.012?μM) exhibited excellent ERα antagonistic activity, its antiproliferative potency in breast cancer MCF-7 cells is equipotent to the approved drug tamoxifen. The fluorescence of compounds 3e and 3f depended on the solvent properties and showed significant changes when mixed with ERα or ERβ in vitro. Furthermore, target molecule 3e could cross the cell membrane, localize and image drug-target interaction in real time without cell washing. Thus, the coumarin-based platform represents a promising new ER-targeted delivery vehicle with potential imaging and therapeutic properties.
- Yang, Lu,Hu, Zhiye,Luo, Junjie,Tang, Chu,Zhang, Silong,Ning, Wentao,Dong, Chune,Huang, Jian,Liu, Xianjun,Zhou, Hai-Bing
-
supporting information
p. 3531 - 3539
(2017/05/29)
-
- Design, synthesis and biological evaluation of novel 3-substituted 4-anilino-coumarin derivatives as antitumor agents
-
Various 3-substituted 4-anilino-coumarin derivatives have been designed, synthesized and their anti-proliferative properties have been studied. The in vitro cytotoxicity screening was performed against MCF-7, HepG2, HCT116 and Panc-1 cancer cell lines by MTT assay. Most of the synthesized compounds exhibited comparable anti-proliferative activity to the positive control 5-Fluorouracil against these four tested cancer cell lines. Among the different substituents at C-3 position of coumarin scaffold, 3-trifluoroacetyl group showed the most promising results. Especially, compounds 33d (IC50?=?16.57, 5.45, 4.42 and 5.16?μM) and 33e (IC50?=?20.14, 6.71, 4.62 and 5.62?μM) showed excellent anti-proliferative activities on MCF-7, HepG2, HCT116 and Panc-1 cell lines respectively. In addition, cell cycle analysis and apoptosis activation revealed that 33d induced G2/M phase arrest and apoptosis in MCF-7 cells in a dose-dependent manner. Low toxicity of compounds 33d and 33e was observed against human umbilical vein endothelial cells (HUVECs), suggesting their acceptable safety profiles in normal cells. Furthermore, the results of in silico ADME studies indicated that both 33d and 33e exhibited good pharmacokinetic properties.
- Luo, Guoshun,Muyaba, Moses,Lyu, Weiting,Tang, Zhichao,Zhao, Ruheng,Xu, Qian,You, Qidong,Xiang, Hua
-
supporting information
p. 867 - 874
(2017/02/18)
-
- Affinity-based small fluorescent probe for NAD(P)H:quinone oxidoreductase 1 (NQO1). Design, synthesis and pharmacological evaluation
-
NQO1 is a dimeric flavoprotein which intimately associated with cancer and overexpressed in the cytosol of numerous human tumor cells. Given that the cellular environment is quite dynamic and versatile, further investigation of the function of NQO1 depends on tools for specific detection of it. Currently, several activity-based assays have been developed to detect NQO1-expressing cancerous tissues. Herein, we report the development of a functional affinity-based small-molecule probe which is composed of a potent small-molecule NQO1 inhibitor 3d as the recognition group, a linker and the fluorophores group FITC. The probe exhibits good inhibitory activity of NQO1 and has been successfully used to label the protein in A549 cells at the micromolar level. These features make the probe favorable for mechanistic studies and cancer diagnostic biomarker. Based on these preliminary results, our laboratory will focus on the further development of fluorescent probe for NQO1, which could be anticipated to be applied in physiological and pathological studies of NQO1.
- Bian, Jinlei,Li, Xiang,Xu, Lili,Wang, Nan,Qian, Xue,You, Qidong,Zhang, Xiaojin
-
p. 828 - 839
(2017/02/10)
-
- Design, synthesis and antifungal activity of coumarin ring-opening derivatives
-
Based on our initial design, we synthesized two series of coumarin ring-opening derivatives by the reactions of hydrolysis and methylation. Results of antifungal screening in vitro showed that the target compounds exhibited potent activity against the six
- Zhang, Ming-Zhi,Zhang, Yu,Wang, Jia-Qun,Zhang, Wei-Hua
-
-
- Design, Synthesis, and Evaluation of in Vitro and in Vivo Anticancer Activity of 4-Substituted Coumarins: A Novel Class of Potent Tubulin Polymerization Inhibitors
-
In this paper, a series of novel 4-substituted coumarin derivatives were synthesized. Among these compounds 34, 39, 40, 43, 62, 65, and 67 exhibited significant antiproliferative activity toward a panel of tumor cell lines at subnanomolar IC50 values. Compound 65 showed potent antiproliferative ability (IC50 values of 7-47 nM) and retained full activity in multidrug resistant cancer cells. Compound 65 caused G2/M phase arrest and interacted with the colchicine-binding site in tubulin, as confirmed by immune-fluorescence staining, microtubule dynamics assays, and competition assays with N,N′-ethylene-bis(iodoacetamide). Compound 65 reduced the cell migration and disrupted capillary-like tube formation in HUVEC cells. Importantly, compound 65 significantly and dose-dependently reduced tumor growth in four xenografts models including paclitaxel sensitive and resistant ovarian tumors (A2780s and A2780/T), adrmicycin sensitive and resistant breast tumors (MCF-7 and MCF-7/ADR), suggesting that compound 65 is a promising novel antimitotic compound for the potential treatment of cancer.
- Cao, Dong,Liu, Yibin,Yan, Wei,Wang, Chunyu,Bai, Peng,Wang, Taijin,Tang, Minghai,Wang, Xiaoyan,Yang, Zhuang,Ma, Buyun,Ma, Liang,Lei, Lei,Wang, Fang,Xu, Bixue,Zhou, Yuanyuan,Yang, Tao,Chen, Lijuan
-
supporting information
p. 5721 - 5739
(2016/07/06)
-
- Microwave-assisted synthesis and antifungal activity of novel coumarin derivatives: Pyrano[3,2-c]chromene-2,5-diones
-
A series of novel fused coumarin analogues pyrano[3,2-c]chromene-2,5-diones have been synthesized through an optimized microwave-assisted protocol. All target compounds were tested and evaluated for their antifungal activity against Botrytis cinerea, Colletotrichum copsica, Alternaria solani, Gibberella zeae and Rhizoctorzia solani. The bioassay results indicated that some of the compounds exhibited potent antifungal activities at concentration less than 50 ppm. For the compounds 5d, 6c and 7b, EC50 values against B. cinerea were as low as 0.141, 0.082 and 0.091 μM, respectively, which represents better antifungal activity than that of the commonly used fungicide Azoxystrobin. Compounds 5d (57%) and 6c (55%) also exhibited more effective control than Azoxystrobin (44%) against Colletotrichum capsica.
- Zhang, Rong-Rong,Liu, Jia,Zhang, Yu,Hou, Meng-Qing,Zhang, Ming-Zhi,Zhou, Fenger,Zhang, Wei-Hua
-
-
- 4 - aromatic amine - coumarin derivatives and its preparation method and medical use (by machine translation)
-
The invention relates to the field of pharmaceutical chemistry, in particular relates to a series of 4?Aromatic amine?Coumarin derivatives, method for their preparation and use in medicine, in particular for the treatment of tumor, such as breast cancer, and the like. The present invention relates to compounds of the general structure is as follows, each group in the formula is defined in the specification. (by machine translation)
- -
-
-
- Natural product Hirtellanine B and its derivatives in the preparation process for the preparation of medicine for treating tumor with the application of the
-
The present invention provides a preparation method of a natural product Hirtellanine B, wherein 2,4,6-trihydroxyacetophenone is adopted as a raw material, and steps of compound a preparation, compound b preparation, compound c preparation, compound d preparation, compound e preparation, compound f preparation, compound g preparation, and the like are performed to prepare the natural product Hirtellanine B. According to the present invention, biological activity screening is performed on Hirtellanine B and 14 Hirtellanine B derivatives, and results show that the natural product Hirtellanine B can inhibit proliferations of Jurkat cells, Raji cells and K562 cells, and the compounds provide a certain inhibition activity for tumor cells. The method has characteristics of easily available raw material, high reaction yield and reasonable operation, and is suitable for industrial production. The Hirtellanine B and the derivatives thereof can be used for preparing tumor treatment drugs, and have great clinical values. The natural product Hirtellanine B preparation method reaction formulas are as the follows.
- -
-
Paragraph 0065; 0137
(2016/10/10)
-
- Microwave-assisted synthesis and antifungal activity of novel fused Osthole derivatives
-
Based on the microwave-assisted synthetic protocol developed in our previous work, we have synthesized a series of novel furo[3,2-c]coumarins as fused Osthole derivatives, via the reaction of 4-hydroxycoumarins and β-ketoesters catalyzed by DMAP. All the target compounds were evaluated in?vitro for their antifungal activity against six phytopathogenic fungi, some compounds exhibited potential activity in the primary assays. Especially compounds 6c, 7b, 8b and 8c (shown in Fig.?1) were the most active ones, EC50values of these four compounds against Colletotrichum capsica, Botrytis cinerea and Rhizoctonia solani were further investigated. 6c was identified as the most promising candidate with the EC50value at 0.110?μM against Botrytis cinerea and 0.040?μM against Colletotrichum capsica, respectively, representing better antifungal activity than that of the commonly used fungicide Azoxystrobin.
- Zhang, Ming-Zhi,Zhang, Rong-Rong,Wang, Jia-Qun,Yu, Xiang,Zhang, Ya-Ling,Wang, Qing-Qing,Zhang, Wei-Hua
-
-
- Combined Claisen Rearrangement and Oxidative Cyclization as a Route to Hydroxymethyl Dihydrofuran-Annulated Coumarins
-
A convenient and simple method for the synthesis of novel 3,4-dihydrofuran-annulated coumarins, 3-(hydroxymethyl)-2H-furo[3,2-c]chromen-4(3H)-ones 5a, 5b, 5c, 5d, 5e, 5f, 5g, by combined Claisen rearrangement and intramolecular regioselective oxidative cyclization of 4-O-allyl coumarin intermediates 3a, 3b, 3c, 3d, 3e, 3f, 3g using inexpensive oxidizing agent m-CPBA is described. The reaction proceeds smoothly by tandem epoxidation/regioselective 5-exo-tet-intramolecular ring opening. The structures of synthesized compounds are established on the basis of spectral data including IR, 1H NMR, and mass and elemental analyses.
- Jayaprakash, Rao Y.,Chakravarthula, Venu
-
p. 1014 - 1018
(2015/08/06)
-
- Synthesis and biological evaluation of 4-(1,2,3-triazol-1-yl)coumarin derivatives as potential antitumor agents
-
In this research, a series of 4-(1,2,3-triazol-1-yl)coumarin conjugates were synthesized and their anticancer activities were evaluated in vitro against three human cancer cell lines, including human breast carcinoma MCF-7 cell, colon carcinoma SW480 cell and lung carcinoma A549 cell. To increase the biological potency, structural optimization campaign was conducted focusing on the C-4 position of 1,2,3-triazole and the C-6, C-7 positions of coumarin. In addition, to further evaluate the role of 1,2,3-triazole and coumarin for antiproliferative activity, 9 compounds possessing 4-(piperazin-1-yl)coumarin framework and 3 derivatives baring quinoline core were also synthesized. By MTT assay in vitro, most of the compounds display attractive antitumor activities, especially 23. Further flow cytometry assays demonstrate that compound 23 exerts the antiproliferative role through arresting G2/M cell-cycle and inducing apoptosis.
- Zhang, Wenjuan,Li, Zhi,Zhou, Meng,Wu, Feng,Hou, Xueyan,Luo, Hao,Liu, Hao,Han, Xuan,Yan, Guoyi,Ding, Zhenyu,Li, Rui
-
p. 799 - 807
(2014/02/14)
-
- Palladium-catalyzed [2+2+1] oxidative annulation of 4-hydroxycoumarins with unactivated internal alkynes: Access to spiro cyclopentadiene-chroman-2,4-dione complexes
-
Herein, we report our new results regarding a palladium-catalyzed [2+2+1] oxidative annulation of 4-hydroxycoumarins with unactivated internal alkynes, which affords a new class of compounds: the spiro cyclopentadiene-chroman-2,4- diones.
- Peng, Shiyong,Gao, Tao,Sun, Shaofa,Peng, Yanhong,Wu, Minghu,Guo, Haibing,Wang, Jian
-
supporting information
p. 319 - 324
(2014/05/20)
-
- Combining silver catalysis and organocatalysis: A sequential michael addition/hydroalkoxylation one-pot approach to annulated coumarins
-
A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.
- Hack, Daniel,Chauhan, Pankaj,Deckers, Kristina,Hermann, Gary N.,Mertens, Lucas,Raabe, Gerhard,Enders, Dieter
-
supporting information
p. 5188 - 5191
(2014/12/11)
-
- Pd-catalyzed allylic alkylation cascade with dihydropyrans: Regioselective synthesis of furo[3,2- c ]pyrans
-
A regioselective palladium-catalyzed allylic alkylation cascade forms furo[3,2-c]pyrans from various cyclic β-dicarbonyl bis-nucleophiles and 3,6-dihydro-2H-pyran bis-electrophiles. The combination of allylic carbonate and anomeric siloxy leaving groups in the dihydropyran substrate allows control of the many regiochemical possibilities in this reaction. Annulation proceeds stereoconvergently to give cis-fused furopyrans from either cis- or trans-substituted starting material.
- Bartlett, Mark J.,Turner, Claire A.,Harvey, Joanne E.
-
p. 2430 - 2433
(2013/07/05)
-
- Palladium-catalyzed oxidative annulation via C-H/N-H functionalization: Access to substituted pyrroles
-
Pyrroles, ubiquitous bioactive heterocycles in nature, are readily prepared via a palladium-catalyzed oxidative annulation of cyclic trans-enamines to various internal alkynes in the absence of a directing group. Copyright
- Peng, Shiyong,Wang, Lei,Huang, Jiayao,Sun, Shaofa,Guo, Haibing,Wang, Jian
-
supporting information
p. 2550 - 2557
(2013/10/21)
-
- Energy transfer in coumarin-sensitised lanthanide luminescence: Investigation of the nature of the sensitiser and its distance to the lanthanide ion
-
A series of lanthanide complexes [Ln(dpxCy)3]3- have been synthesised. The ligands are composed of a coordinating dipicolinic acid backbone decorated with a polyoxyethylene arm fitted with a coumarin moiety at its extremity. The nature of the coumarin as well as the length of the linker have been varied. Upon excitation at 320 nm, the coumarin exclusively acts as an antenna while the dipicolinic acid core is not excited. Upon excitation below 300 nm, both parts are excited. With europium as a metal centre, the relaxation of the europium ion (intrinsic quantum yield ΦEuEu and radiative lifetime τr) is constant for all the studied ligands. Therefore, the observed differences in overall quantum yield (ΦEuL) in such systems come exclusively from the variation of the terminal coumarin. The overall quantum yields of the studied complexes are low (ΦEuL sens), the distance between the coumarin sensitiser and the lanthanide centre was explored in solution and compared to the solid state. In the solid state, a dramatic effect was confirmed, with an improvement of 80% in the quantum yield ΦEuL for short linkers ((-CH2CH2O-)n with n = 1 compared to n = 3). By monitoring the lifetime decay of the excited state of the lanthanide cation with nanosecond vs. microsecond time-resolved spectroscopy at low temperature, the sensitisation of the lanthanide ions by coumarin derivatives was demonstrated to mainly occur through the singlet excited state of the coumarin and not via the usual triplet pathway. No evidence of a different behaviour at room temperature was found by transient triplet-triplet absorption spectroscopy.
- Andres, Julien,Chauvin, Anne-Sophie
-
p. 15981 - 15994
(2013/09/24)
-
- Studies in synthesis and tautomerism of new warfarin derivatives
-
Substituted 4-hydroxy-7-methoxy-benzopyran-2-(/-V)-one on Michael condensation with different a,p-unsaturated ketones gave various warfarin derivatives. 1H NMR studies of these compounds in deuteriochloroform showed three interconverting tautomeric structures, two of which are cyclic diastereomeric hemiketals, while the third one is the open chain intermediate form; whereas the 1H NMR in deuteriodimethylsulfoxide shows existence of only two diastereomeric hemiketal forms.
- Soman, Shubhangi S.,Patel,Jethawa, Komal B.,Baloni, Radhika
-
p. 233 - 236
(2013/09/24)
-
- Mapping the ATP-binding domain of DNA-dependent protein kinase (DNA-PK) with coumarin- and isocoumarin-derived inhibitors
-
Replacement of the core heterocycle of a defined series of chromen-4-one DNA-PK inhibitors by the isomeric chromen-2-one (coumarin) and isochromen-1-one (isocoumarin) scaffolds was investigated. Structure-activity relationships for DNA-PK inhibition were broadly consistent, albeit with a reduction of potency compared with the parent chromenone.
- Payne, Sara L.,Rodriguez-Aristegui, Sonsoles,Bardos, Julia,Cano, Celine,Golding, Bernard T.,Hardcastle, Ian R.,Peacock, Marcus,Parveen, Nahida,Griffin, Roger J.
-
scheme or table
p. 3649 - 3653
(2010/09/17)
-
- Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: Quinone oxidoreductase-1 (NQO1)
-
The synthesis is reported here of two novel series of inhibitors of human NAD(P)H quinone oxidoreductase-1 (NQO1), an enzyme overexpressed in several types of tumor cell. The first series comprises substituted symmetric dicoumarol analogues; the second series contains hybrid compounds where one 4-hydroxycoumarin systemis replaced by a different aromatic moiety. Several compounds show equivalent or improved NQO1 inhibition over dicoumarol, both in the presence and in the absence of added protein. Further, correlation is demonstrated between the ability of these agents to inhibit NQO1 and computed binding affinity. We have solved the crystal structure of NQO1 complexed to a hybrid compound and find good agreement with the in silico model. For both MIA PaCa-2 pancreatic tumor cells and HCT116 colon cancer cells, dicoumarol shows the greatest toxicity of all compounds. Thus, we provide a computational, synthetic, and biological platform to generate competitive NQO1 inhibitors with superior pharmacological properties to dicoumarol. This will allow a more definitive study of NQO1 activity in cells, in particular, its drug activating/detoxifying properties and ability to modulate oncoprotein stability. 2009 American Chemical Society.
- Nolan, Karen A.,Doncaster, Jeremy R.,Dunstan, Mark S.,Scott, Katherine A.,Frenkel, A. David,Siegel, David,Ross, David,Barnes, John,Levy, Colin,Leys, David,Whitehead, Roger C.,Stratford, Ian J.,Bryce, Richard A.
-
experimental part
p. 7142 - 7156
(2010/07/20)
-
- Selective benzopyranone and pyrimido[2,1-α]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: Synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro
-
A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 μM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2′-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 μM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 μM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.
- Griffin, Roger J.,Fontana, Gabriele,Golding, Bernard T.,Guiard, Sophie,Hardcastle, Ian R.,Leahy, Justin J. J.,Martin, Niall,Richardson, Caroline,Rigoreau, Laurent,Stockley, Martin,Smith, Graeme C. M.
-
p. 569 - 585
(2007/10/03)
-
- Condensation of 2-hydroxyacetophenones with trichloroacetonitrile as a route to 2-trichloromethylchromones and 4-hydroxycoumarins
-
Condensation of 2-hydroxyacetophenones with trichloroacetonitrile in the presence of N-methylanilinomagnesium bromide affords hydroxyaryl β-amino-β-trichloromethylvinyl ketones, which are converted into 2-trichloromethylchromones upon treatment with concentrated HCl. The resulting compounds react with alcoholic solutions of NH3 or KOH to form 3-amino-1-(2-hydroxyaryl)-4,4,4-trichlorobut-2-en-1-ones and 4-hydroxycoumarins, respectively.
- Sosnovskikh,Kutsenko,Ovsyannikov
-
p. 478 - 481
(2007/10/03)
-
- Facile Synthesis of 4-Hydroxycoumarins by Sulfur-Assisted Carbonylation of 2'-Hydroxyacetophenones with Carbon Monoxide
-
4-Hydroxycoumarins (4-hydroxy-2-oxo-2H-1-benzopyrans) were synthesized in good to excellent yields by C-carbonylation of 2'-hydroxyacetophenones with carbon monoxide in the presence of sulfur and bases.This is the first example of sulfur-assisted C-carbonylation with carbon monoxide.
- Mizuno, Takumi,Nishiguchi, Ikuzo,Hirashima, Tsuneaki,Ogawa, Akiya,Kambe, Nobuaki,Sonoda, Noboru
-
p. 257 - 259
(2007/10/02)
-
- SELENIUM ASSISTED CARBONYLATION OF ALKYL ARYL KETONES WITH CARBON MONOXIDE
-
Selenium assisted carbonylation of alkyl aryl ketones with carbon monoxide leading to formation of 1,3-dicarbonyl compounds as C-carbonylated products is described. o-Hydroxyacetophenone (7a) and its derivatives (7b, 7c and 7d) have been converted to the corresponding 4-hydroxycoumarins (8a, 8b, 8c and 8d) in moderate to quantitative yields by treatment with an equivalent of selenium and carbon monoxide with concomitant formation of hydrogen selenide (9) (Eq.(8)).It was further revealed that oxidation of in situ formed hydrogen selenide to selenium with an appropriate oxidizing agent such as nitrobenzene permitted catalytic use of selenium for the carbonylation of 7.Possible rationalizations for the formation of 4-hydroxycoumarins are suggested.
- Ogawa, Akiya,Kambe, Nobuaki,Murai, Shinji,Sonoda, Noboru
-
p. 4813 - 4820
(2007/10/02)
-
- Coumarin derivatives for the treatment of allergies
-
Pharmaceutical compositions for the treatment of allergies are produced using coumarin derivatives as the active agent. Certain of these compounds and their salts are novel.
- -
-
-