- Synthesis, antimicrobial and antioxidant activities of 5-((2-oxo-2H- chromen-7-yloxy)methyl)-1,3,4-thiadiazol-2(3H)-one derived from umbelliferone
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5-((2-Oxo-2H-chromen-7-yloxy)methyl)-1,3,4-thiadiazol-2(3H)-one was synthesized and characterized by FT-IR and NMR spectra in addition to elemental analysis. The prepared compound shows considerable antibacterial and antifungal activity. The free radical scavenging activity of the synthesized compound was screened for in vitro antioxidant activity.
- Al-Amiery, Ahmed A.,Al-Temimi, Ali A.,Sulaiman, Ghassan M.,Aday, Hamdan A.,Kadhum, Abdul Amir Hassan,Mohamad, Abu Bakar
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- Coumarins as potential antioxidant agents complemented with suggested mechanisms and approved by molecular modeling studies
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Syntheses of coumarins, which are a structurally interesting antioxidant activity, was done in this article. The modification of 7-hydroxycoumarin by different reaction steps was done to yield target compounds. Molecular structures were characterized by different spectroscopical techniques (Fourier transformation infrared and nuclear magnetic resonance). Antioxidant activities were performed by using various in vitro spectrophometric assays against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and hydrogen peroxide (H2O2). All compounds exhibited high efficiency as antioxidants compared to ascorbic acid. The highest efficiency scavenging activity was found for compound 3 (91.0 ± 5.0), followed by compounds 2 and 4 (88.0 ± 2.00; and 87.0 ± 3.00). Ascorbic acid C was used as a standard drug with a percentage inhibition of 91.00 ± 1.5. The mechanism of the synthesized compounds as antioxidants was also studied. Hartree-Fock-based quantum chemical studies have been carried out with the basis set to 3-21G, in order to obtain information about the three-dimensional (3D) geometries, electronic structure, molecular modeling, and electronic levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), to understand the antioxidant activity for the synthesized compounds.
- Al-Majedy, Yasameen K.,Al-Duhaidahawi, Dunya L.,Al-Azawi, Khalida F.,Al-Amiery, Ahmed A.,Kadhum, Abdul Amir H.,Mohamad, Abu Bakar
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- Dual P-glycoprotein and CA XII inhibitors: A new strategy to reverse the P-gp Mediated Multidrug Resistance (MDR) in cancer cells y
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A new series of N,N-bis(alkanol)amine aryl diesters was synthesized and studied as dual P-glycoprotein (P-gp) and carbonic anhydrase XII inhibitors (CA XII). These hybrids should be able to synergistically overcome P-gp mediated multidrug resistance (MDR) in cancer cells. It was reported that the effux activity of P-gp could be modulated by CA XII, as the pH reduction caused by CA XII inhibition produces a significant decrease in P-gp ATPase activity. The new compounds reported here feature both P-gp and CA XII binding moieties. These hybrids contain a N,N-bis(alkanol)amine diester scaffold found in P-glycoprotein ligands and a coumarin or benzene sulfonamide moiety to target CA XII. Many compounds displayed a dual activity against P-gp and CA XII being active in the Rhd 123 uptake test on K562/DOX cells and in the hCA XII inhibition test. On LoVo/DOX cells, that overexpress both P-gp and CA XII, some coumarin derivatives showed a high MDR reversal effect in Rhd 123 uptake and doxorubicin cytotoxicity enhancement tests. In particular, compounds 7 and 8 showed higher activity than verapamil and were more potent on LoVo/DOX than on K562/DOX cells overexpressing only P-gp. They can be considered as valuable candidates for selective P-gp/CA XII inhibition in MDR cancer cells.
- Bartolucci, Gianluca,Braconi, Laura,Bua, Silvia,Coronnello, Marcella,Dei, Silvia,Lapucci, Andrea,Manetti, Dina,Romanelli, Maria Novella,Supuran, Claudiu T.,Teodori, Elisabetta
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- Combination of 7-hydroxycoumarin in a platinum(IV) complex derived from cisplatin enhanced cytotoxicity with multiple mechanisms of action
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A novel compound, Cou-platin, composed of 7-hydroxycoumarin and a platinum(IV) moiety derived from cisplatin was designed and synthesized. Significantly, Cou-platin exhibited more potent in vitro antitumor activity against all tested cancer cell lines than that of cisplatin, which was mainly attributed to the liberation of cisplatin and 7-hydroxycoumarin upon reduction with a biomolecular agent. Besides, cellular accumulation of Cou-platin was dramatically increased among several cancer cells in contrast to cisplatin. Flow cytometry study revealed that Cou-platin arrested cell cycle at G2 phase and induced cell apoptosis. Western blots results indicated that it not only activated cell apoptosis pathway, but also inhibited extracellular regulated protein kinases/mitogen-activated protein kinase pathway. In vivo tests showed that Cou-platin, at equimolar dose to cisplatin, could inhibit tumor growth in nude mouse HCT116 tumor xenograft models almost as cisplatin and oxaliplatin, but with less toxicity.
- Hua, Wuyang,Zhao, Jian,Hu, Weiwei,Gou, Shaohua
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- A dual-mode molecular switch based on a chiral binaphthol-coumarin compound
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A dual-mode, efficient molecular switching system based on photomodulation of optical rotational power and fluorescence emission of a chiral binaphthol-coumarin compound is presented. (C) 2000 Elsevier Science Ltd.
- Birau, Maria M.,Yuan Wang, Zhi
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- Novel 6- and 7-substituted coumarins with inhibitory action against lipoxygenase and tumor-associated carbonic anhydrase IX
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A series of carboxamide derivatives of 6- and 7-substituted coumarins have been prepared by an original procedure starting from the corresponding 6- or 7-hydroxycoumarins which were alkylated with ethyl iodoacetate, and the obtained ester was converted to the corresponding carboxylic acids which were thereafter reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the desired amides. The new derivatives were investigated as inhibitors of two enzymes, human carbonic anhydrases (hCAs) and soy bean lipoxygenase (LOX). Compounds 4a and 4b were potent LOX inhibitors, whereas many effective hCA IX inhibitors (KIs in the range of 30.2–30.5 nM) were detected in this study. Two compounds, 4b and 5b, showed the phenomenon of dual inhibition. Furthermore, these coumarins did not significantly inhibit the widespread cytosolic isoforms hCA I and II, whereas they were weak hCA IV inhibitors, making them hCA IX-selective inhibitors. As hCA IX and LOX are validated antitumor targets, these results are promising for the investigation of novel drug targets involved in tumorigenesis.
- Peperidou, Aikaterini,Bua, Silvia,Bozdag, Murat,Hadjipavlou-Litina, Dimitra,Supuran, Claudiu T.
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- Novel silver(I) complexes of coumarin oxyacetate ligands and their phenanthroline adducts: Biological activity, structural and spectroscopic characterisation
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Novel silver(I) complexes of coumarin oxyacetate ligands and their phenanthroline adducts have been prepared and characterised by microanalytical data and spectroscopic techniques (IR, 1H, 13C NMR, UV–Vis). The crystal structure of one Ag(I) complex was determined by X-ray diffraction analysis. The experimental spectroscopic data have been interpreted on the basis of molecular structure modeling and subsequent spectra simulation with density functional theory method. The binding modes of the coumarins and phenanthroline ligands (monodentate, bidentate, bridging) to Ag(I) have been theoretically modelled and discussed as to the most probable ligand binding in the series of complexes studied. The antimicrobial and antifungal activities have been determined and the complexes were found to have mostly moderate antibacterial activity but some of the phenanthroline adducts were found to have antifungal activity against the clinically important fungus C. albicans, comparable to that of the commercial agents, Amphotericin B and Ketoconazole. Preliminary investigations into the possible mechanism of action of the silver complexes indicated that they did not interact with DNA via nuclease activity or intercalation but the ability to act as a superoxide dismutase mimetic may be related to their antimicrobial activity.
- Mujahid, Muhammad,Trendafilova, Natasha,Arfa-Kia, Agnieszka Foltyn,Rosair, Georgina,Kavanagh, Kevin,Devereux, Michael,Walsh, Maureen,McClean, Siobhán,Creaven, Bernadette S.,Georgieva, Ivelina
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- Anticancer drug delivery of PEG based micelles with small lipophilic moieties
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Herein, we reported a new type of self-assembly micelles based on amphiphilic polymers of cinnamate and coumarin derivatives modified PEG for drug delivery applications. Lipophilic cinnamic acid (CIN) and 7-carboxyl methoxycoumarin (COU) were immobilized on the terminal groups of poly(ethylene glycol) (PEG) to prepare amphiphiles. The amphiphiles self-assembled into micelles. The amphiphiles and micelles were characterized by 1H NMR, FT-IR, DLS and TEM. Doxorubicin (DOX) was used as a model drug to investigate the lipophilic moieties effects on the drug release behaviors. The DOX loaded micelles were incubated with HepG2 liver cancer cells to study the in vitro anticancer activities. The results showed that DOX could be encapsulated in the micelles efficiently. The mean diameter of the drug loaded micelles was around 100 nm. Drug release profile revealed that the release rate of DOX loaded COU-PEG-COU micelles was significantly slower than that of CIN-PEG-CIN micelles. The DOX loaded micelles could be internalized in HepG2 cells. Both CLSM and flow cytometry results showed that the DOX loaded CIN-PEG-CIN micelles exhibited better anticancer efficacy. Crown Copyright
- Lei, Ying,Lai, Yusi,Li, Yuanlin,Li, Sai,Cheng, Gang,Li, Dong,Li, Haiping,He, Bin,Gu, Zhongwei
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- A new convenient route to 2-oxoethoxycoumarins: Key intermediates in the synthesis of natural products
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A new synthetic route to coumarinyloxyaldehydes starting from hydroxycoumarins is presented; these compounds, useful intermediates in the preparation of natural products such as geiparvarin and psoralens, are now available in excellent yields with a simple workup procedure. Moreover the reported route has been applied to dihydroxycoumarins.
- Chimichi, Stefano,Boccalini, Marco,Cosimelli, Barbara
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- Construction of Dual Stimuli-Responsive Platinum(IV) Hybrids with NQO1 Targeting Ability and Overcoming Cisplatin Resistance
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Quinone oxidoreductase isozyme I (NQO1) is a cytoprotective two-electron-specific reductase that highly expresses in various cancer cells. Taking NQO1 as the target, we herein report three hybrid compounds from Pt(IV) complexes and a quinone propionic aci
- Fang, Lei,Qin, Xiaodong,Zhao, Jian,Gou, Shaohua
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- Anti-Inflammatory Effect of Novel 7-Substituted Coumarin Derivatives through Inhibition of NF-κB Signaling Pathway
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A series of novel 7-substituted coumarin derivatives were synthesized and evaluated. Biological screening results obtained by the evaluation of the compounds’ inhibition against LPS-induced IL-6 and TNF-α release in RAW 264.7 cells indicated that most compounds exhibited potent anti-inflammatory activity. Among them, N-(3-methoxybenzyl)-2-[(2-oxo-2H-chromen-7-yl)oxy]acetamide (2d) showed the best activity. The potential targets of title compound 2d were reversely screened with the molecular modeling software, Discovery Studio 2017 R2. Screening and molecule docking results showed that 2d could bind to the active site (NLS Polypeptide) of NF-κB p65, and this binding affinity was confirmed by surface plasmon resonance (SPR) analysis. Furthermore, Western blot assay showed that 2d remarkably blocked the NF-κB signaling pathway in vitro. Collectively, all these findings suggested that compound 2d might be a promising lead compound worthy of further pursuit.
- Mu, Chaoyu,Wu, Mingfei,Li, Zeng
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- Anticancer Activity of Bifunctional Organometallic Ru(II) Arene Complexes Containing a 7-Hydroxycoumarin Group
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Three organometallic Ru(arene) compounds bearing 7-hydroxycoumarin have been designed and synthesized. Resulting Ru(II) complexes 2-4 showed potent cytotoxicity against the tested cancer cell lines, much higher than either the ligand L1 or unfunctionalized complex 1 alone. Further study indicated complexes 2-4 can activate the expression of Bax, induce cytochrome c release from the mitochondria, and finally activate caspase-3, hinting that these compounds probably induce cell apoptosis by mitochondrial pathway. Additional molecular docking study showed that complexes 2-4 have the potential to bind with the MEK1, and Western blot analysis confirmed that the Ru(II) complexes can prevent the phosphorylation of MEK1 and ERK1 in HCT116 cells, which helps us to further understand the anticancer mechanisms of the newly synthesized complexes. Overall, our research suggested that the ruthenium-coumarin complexes could induce cell apoptosis via inhibition of the mitochondrial and ERK signal pathways.
- Zhao, Jian,Zhang, Dingyi,Hua, Wuyang,Li, Wanchun,Xu, Gang,Gou, Shaohua
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- Synthesis and Biological Evaluation of Substituted Indole and Its Analogs as Influenza A Virus Inhibitors
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Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds D1, D3, D9, G1, G3, G12 and G23 were identified as promising anti-IAV candidates with excellent anti-IAV efficacy (IC50 values of 3.06–5.77 μm) and low cytotoxicity (CC50 values up to and beyond 100 μm). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization.
- Zhang, Xuandi,Zhang, Guo-Ning,Wang, Yujia,Zhu, Mei,Wang, Juxian,Li, Ziqiang,Li, Donghui,Cen, Shan,Wang, Yucheng
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- Theranostic Pt(IV) Conjugate with Target Selectivity for Androgen Receptor
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It is difficult to diagnose and treat castration-resistant prostate cancer (CRPC) which occurs due to the overexpression of androgen receptor (AR). Because there is a high level of AR in CRPC, we designed and prepared three Pt(IV)-based prodrugs targeting AR. Among them, compound 3, a three-in-one hybrid (an AR binding ligand, a cisplatin unit, and a coumarin moiety), was found to display satisfactory AR binding affinity and antagonist activity against androgen receptor, which could also be effectively internalized and visualized in LNCaP (AR+) cells. Due to its AR affinity, 3 selectively accumulated in greater quantities in LNCaP (AR+) cells than in PC-3 (AR-) cells. Moreover, compound 3 exhibited excellent anticancer activity superior to cisplatin.These results highlight the targeting theranostic application of Pt(IV) prodrugs.
- Qin, Xiaodong,Fang, Lei,Zhao, Jian,Gou, Shaohua
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p. 5019 - 5029
(2018/05/22)
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- Synthesis and anti-acetylcholinesterase activity of N-[(indolyl)ethyl)- coumarin-yloxy)]alkanamides
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Novel coumarin-tryptamine systems attached through a linker were synthesised and evaluated in vitro against acetylcholinesterase by the classical Ellman's test.
- Ghanei-Nasab, Sarah,Nadri, Hamid,Moradi, Alireza,Marjani, Azam,Shabani, Shabnam,Firoozpour, Loghman,Moghimi, Setareh,Khoobi, Mehdi,Hadizadeh, Farzin,Foroumadi, Alireza
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p. 120 - 123
(2017/03/15)
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- An Efficient One-Pot Synthesis of 2-(Aryloxyacetyl)cyclohexane-1,3-diones as Herbicidal 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors
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4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is an important target for new bleaching herbicides discovery. As a continuous work to discover novel crop selective HPPD inhibitor, a series of 2-(aryloxyacetyl)cyclohexane-1,3-diones were rationally designed and synthesized by an efficient one-pot procedure using N,N′-carbonyldiimidazole (CDI), triethylamine, and acetone cyanohydrin in CH2Cl2. A total of 58 triketone compounds were synthesized in good to excellent yields. Some of the triketones displayed potent in vitro Arabidopsis thaliana HPPD (AtHPPD) inhibitory activity. 2-(2-((1-Bromonaphthalen-2-yl)oxy)acetyl)-3-hydroxycyclohex-2-en-1-one, II-13, displayed high, broad-spectrum, and postemergent herbicidal activity at the dosage of 37.5-150 g ai/ha, nearly as potent as mesotrione against some weeds. Furthermore, II-13 showed good crop safety against maize and canola at the rate of 150 g ai/ha, indicating that II-13 might have potential as a herbicide for weed control in maize and canola fields. II-13 is the first HPPD inhibitor showing good crop safety toward canola.
- Wang, Da-Wei,Lin, Hong-Yan,He, Bo,Wu, Feng-Xu,Chen, Tao,Chen, Qiong,Yang, Wen-Chao,Yang, Guang-Fu
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p. 8986 - 8993
(2016/12/09)
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- Writing and erasing hidden optical information on covalently modified cellulose paper
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An unprecedented strategy for preparing photoresponsive cellulose paper enabling the storage of short-lived optical data by covalent photopatterning is disclosed. An ab initio design hinting that the covalent grafting of coumarins on the paper could yield valuable photoresponsive units was first performed. Second, light sensitive paper that can be reversibly altered upon irradiation at a specific wavelength was prepared by covalent surface functionalization with coumarins. Third, the validity of this strategy is demonstrated using the photolithography of several gripping patterns such as a dynamic QR code.
- D'Halluin,Rull-Barrull,Le Grognec,Jacquemin,Felpin
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p. 7672 - 7675
(2016/07/06)
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- Photodimerisation of a coumarin-dipeptide gelator
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Here we report a coumarin based hydrogelator that can form bulk gels, or homogeneous thin gels via an electrochemical pH drop. The gel can then be strengthened by post-gelation photodimerisation of the coumarin groups by irradiating with UV light.
- Draper, Emily R.,McDonald, Tom O.,Adams, Dave J.
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supporting information
p. 12827 - 12830
(2015/08/06)
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- Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives
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A series of 7-hydroxycoumarin derivatives connected by an amidic linker to the different amines were designed and synthesized as cholinesterase inhibitors. Most compounds showed remarkable inhibitory activity against acetylcholinesterase (AChE) and butyry
- Alipour, Masoumeh,Khoobi, Mehdi,Moradi, Alireza,Nadri, Hamid,Homayouni Moghadam, Farshad,Emami, Saeed,Hasanpour, Zeinab,Foroumadi, Alireza,Shafiee, Abbas
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p. 536 - 544
(2014/07/07)
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- Hybrids of phenylsulfonylfuroxan and coumarin as potent antitumor agents
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Sixteen furoxan-based nitric oxide (NO) releasing coumarin derivatives (6a-c, 8a-g, 10a, 13a,b, 15, and 17a,b) were designed, synthesized, and evaluated against the A549, HeLa, A2780, A2780/CDDP, and HUVEC cell lines. Most derivatives displayed potent antiproliferation activities. Among them, 8b exhibited the strongest antiproliferation activity on the four sensitive cell lines mentioned above and three drug resistant tumor cell lines A2780/CDDP, MDA-MB-231/Gem, and SKOV3/CDDP with IC50 values from 14 to 53 nM and from 62 to 140 nM, respectively. Furthermore, 8b inhibited the growth of A2780 in vivo and displayed lower toxicity on nontumorigenesis T29, showing good selectivity against malignant cells in vitro. Preliminary pharmacological studies showed that 8b induces apoptosis, arrests the cell cycle at the G2/M phase in the A2780 cell line, and disrupts the phosphorylation of MEK1 and ERK1. Overall, the NO-releasing capacity and the inhibition of ERK/MAPK pathway signaling may explain the potent antineoplastic activity of these compounds.
- Liu, Ming-Ming,Chen, Xiao-Yu,Huang, Yao-Qing,Feng, Pan,Guo, Ya-Lan,Yang, Gong,Chen, Ying
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p. 9343 - 9356
(2015/01/09)
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- Water-soluble o-hydroxycinnamate as an efficient photoremovable protecting group of alcohols with fluorescence reporting
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Two new o-hydroxycinnamates have been prepared for photoremovable protecting groups, and their photochemistry has been investigated. The photolysis of two caged compounds can efficiently release the corresponding alcohol in aqueous solutions, and the unca
- Duan, Xue-You,Zhai, Bao-Chang,Song, Qin-Hua
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p. 593 - 598
(2012/06/29)
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- The use of umbelliferone in the synthesis of new heterocyclic compounds
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New coumarin derivatives, namely 7-[(5-amino-1,3,4-thiadiazol-2-yl)methoxy] - 2H-chromen-2-one (4), 5-[(2-oxo-2H-chromen-7-yloxy)methyl]-1,3,4-thiadiazol- 2(3H)- one (5), 2-[2-(2-oxo-2H-chromen-7-yloxy)acetyl]-N- phenylhydrazinecarbothioamide (7), 7-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl) methoxy]-2H-chromen-2-one (8) and 7-[(5- mercapto-4-phenyl-4H-1,2,4-triazol-3- yl)methoxy]-2H-chromen-2-one (9) were prepared starting from the natural compound umbelliferone (1). The newly synthesized compounds were characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR).
- Al-Amiery, Ahmed A.,Musa, Ahmed Y.,Kadhum, Abdul Amir H.,Mohamad, Abu Bakar
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p. 6833 - 6843
(2011/10/31)
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- Inhibitors of DNA polymerase β: Activity and mechanism
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Bioassay-guided fractionation of extracts prepared from Couepia polyandra and Edgeworthia gardneri resulted in the isolation of the DNA polymerase β (pol β) inhibitors oleanolic acid (1), edgeworin (2), betulinic acid (3), and stigmasterol (4). Study of these pol β inhibitors revealed that three of them inhibited both the lyase and polymerase activities of DNA polymerase β, while stigmasterol inhibited only the lyase activity. Further investigation indicated that the four inhibitors had substantially different effects on the DNA-pol β binary complex that is believed to be an obligatory intermediate in the lyase reaction. It was found that the inhibitors potentiated the inhibitory action of the anticancer drug bleomycin in cultured A549 cells, without any influence on the expression of pol β in the cells. The results of the unscheduled DNA synthesis assay support the thesis that the potentiation of bleomycin cytotoxicity by DNA pol β inhibitors was a result of an inhibition of DNA repair synthesis.
- Gao, Zhijie,Maloney, David J.,Dedkova, Larisa M.,Hecht, Sidney M.
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p. 4331 - 4340
(2008/12/20)
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- Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction
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In order to find novel nonsteroidal compounds possessing an inhibitory activity against delayed-type hypersensitivity (DTH) reactions, we conducted random screening using a picryl chloride (PC)-induced contact hypersensitivity reaction (CHR) in mice, and found compound 1 as a lead compound. Then we synthesized and evaluated an extensive series of 5-carboxamidouracil derivatives focused on both the uracil and the antioxidative moieties. Among them, we found that the hindered phenol moiety was necessary to exhibit the activities; especially, compounds 28a-28c having the partial structure of vitamin E were found to exert potent activities against the DTH reaction by both oral and topical administration. And compound 28c showed antioxidative activity against lipid peroxidation with an IC50 of 5.9μM. Compound 28c (CX-659S) was chosen as a candidate drug for the treatment of cutaneous disorders such as atopic dermatitis and allergic contact dermatitis. Copyright (C) 2000 Elsevier Science Ltd.
- Tobe, Masanori,Isobe, Yoshiaki,Goto, Yuso,Obara, Fumihiro,Tsuchiya, Masami,Matsui, Junko,Hirota, Kosaku,Hayashi, Hideya
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p. 2037 - 2047
(2007/10/03)
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