- Synthesis and anticancer activity of chalcone–quinoxalin conjugates
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Two series of quinoxaline–chalcone conjugates have been prepared by aldolic condensation and aromatic nucleophilic substitution reaction, and their anticancer activity against three cancer cell lines including benign prostatic hyperplasia epithelial cell (BPH-1), neuron-like rat pheochromocytoma cell line (PC12) and human breast cancer cell line (MCF-7) were evaluated in?vitro. All of the synthesized compounds exhibited moderate to good activity against the cancer cell lines selected. Particularly, Compound A5 showed the excellent potent activity against BPH-1 and MCF-7 with IC50 values of 10.4 and 9.1 μM, respectively, which is similar to doxorubicin (14.1 and 9.2 μM, respectively). As well as compound B6 exhibited most excellent activity toward PC12 with IC50 values of 16.4 μM. Compound A10 exhibited 55.4, 36.8 and 54.5 folds higher selectivity for BPH-1, PC12 and MCF-7 cells than for HEK-293 cell, respectively. In addition, theoretical biological activities of compounds A5 and A10 were evaluated by SwissADME.
- Ma, Xiaoyun,Wang, Daoping,Wei, Gang,Zhou, Qingdi,Gan, Xiuhai
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- Synthesis and antiprotozoal activity of furanchalcone–quinoline, furanchalcone–chromone and furanchalcone–imidazole hybrids
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We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of several furanchalcone–quinoline, furanchalcone–chromone, and furanchalcone–imidazole hybrids. The synthesized compounds were evaluated against ama
- García, Elisa,Coa, Juan C.,Otero, Elver,Carda, Miguel,Vélez, Iván D.,Robledo, Sara M.,Cardona, Wilson I.
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- New class of hybrids based on chalcone and melatonin: a promising therapeutic option for the treatment of colorectal cancer
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Considering that conventional chemotherapy provides only a limited increase of overall survival for patients with colorectal cancer (CRC), and resistance is a major cause of therapeutic failure, the emergence of new therapies is needed. Development of dif
- Arias, Juan D.,Cardona-G, Wilson,Herrera-R, Angie,Moreno, Gustavo,Yepes, Andrés F.
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p. 2240 - 2255
(2021/10/20)
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- Efficient solvent- And temperature-tuned access to aldoxime ethers and phenolic functions by Pd-catalyzed C-O cross-coupling of aldoximes with aryl bromides and bromo-chalcones
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A single method with a functionality switching option was developed for the first time for the Pd-catalyzed C-O cross-coupling of aryl bromides and bromo-chalcones with aldoximes. The ligand tBuXPhos (L2) was found to be an effective supporting ligand for the Pd-catalyzed coupling of aldoximes with bromo coupling partners. The functionality switching from oxime ethers to a phenolic or hydroxy group was driven by solvent or temperature. This method offers the products in good to excellent yields in short reaction times.
- Reeta,Rangarajan,Kaushik, Kumar,Singh, Rishi Pal,Singh, Manjula,Singh, Raj Pal
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supporting information
p. 1326 - 1336
(2020/02/11)
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- Small multitarget molecules incorporating the enone moiety
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Chalcones represent a class of small drug/druglike molecules with different and multitarget biological activities. Small multi-target drugs have attracted considerable interest in the last decade due their advantages in the treatment of complex and multifactorial diseases, since “one drug-one target” therapies have failed in many cases to demonstrate clinical efficacy. In this context, we designed and synthesized potential new small multi-target agents with lipoxygenase (LOX), acetyl cholinesterase (AChE) and lipid peroxidation inhibitory activities, as well as antioxidant activity based on 2-/4- hydroxy-chalcones and the bis-etherified bis-chalcone skeleton. Furthermore, the synthesized molecules were evaluated for their cytotoxicity. Simple chalcone b4 presents significant inhibitory activity against the 15-human LOX with an IC50 value 9.5 μM, interesting anti-AChE activity, and anti-lipid peroxidation behavior. Bis-etherified chalcone c12 is the most potent inhibitor of AChE within the bis-etherified bis-chalcones followed by c11. Bis-chalcones c11 and c12 were found to combine anti-LOX, anti-AchE, and anti-lipid peroxidation activities. It seems that the anti-lipid peroxidation activity supports the anti-LOX activity for the significantly active bis-chalcones. Our circular dichroism (CD) study identified two structures capable of interfering with the aggregation process of Aβ. Compounds c2 and c4 display additional protective actions against Alzheimer’s disease (AD) and add to the pleiotropic profile of the chalcone derivatives. Predicted results indicate that the majority of the compounds with the exception of c11 (144 ?) can cross the Blood Brain Barrier (BBB) and act in CNS. The results led us to propose new leads and to conclude that the presence of a double enone group supports better biological activities.
- Liargkova, Thalia,Eleftheriadis, Nikolaos,Dekker, Frank,Voulgari, Efstathia,Avgoustakis, Constantinos,Sagnou, Marina,Mavroidi, Barbara,Pelecanou, Maria,Hadjipavlou-Litina, Dimitra
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- Novel chalcone and flavone derivatives as selective and dual inhibitors of the transport proteins ABCB1 and ABCG2
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During cancer chemotherapy, certain cancers may become cross-resistant to structurally diverse antineoplastic agents. This so-called multidrug resistance (MDR) is highly associated with the overexpression of ATP-binding cassette (ABC) transport proteins. These membrane-bound efflux pumps export a broad range of structurally diverse endo- and xenobiotics, including chemically unrelated anticancer agents. This translocation of drugs from the inside to the outside of cancer cells is mediated at the expense of ATP. In the last 40 years, three ABC transporters – ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) – have mainly been attributed to the occurrence of MDR in cancer cells. One of the strategies to overcome MDR is to inhibit the efflux transporter function by small-molecule inhibitors. In this work, we investigated new chalcone- and flavone-based compounds for selective as well as broad-spectrum inhibition of the stated transport proteins. These include substituted chalcones with variations at rings A and B, and flavones with acetamido linker at position 3. The synthesized molecules were evaluated for their inhibitory potential against ABCB1, ABCC1, and ABCG2 in calcein AM and pheophorbide A assays. In further investigations with the most promising candidates from each class, we proved that ABCB1- and ABCG2-mediated MDR could be reversed by the compounds. Moreover, their intrinsic toxicity was found to be negligible in most cases. Altogether, our findings contribute to the understanding of ABC transport proteins and reveal new compounds for ongoing evaluation in the field of ABC transporter-mediated MDR.
- Silbermann, Katja,Shah, Chetan P.,Sahu, Niteshkumar U.,Juvale, Kapil,Stefan, Sven Marcel,Kharkar, Prashant S.,Wiese, Michael
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p. 193 - 213
(2019/01/03)
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- Novel chalcone derivatives containing a 1,2,4-triazine moiety: Design, synthesis, antibacterial and antiviral activities
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A series of novel chalcone derivatives containing the 1,2,4-triazine moiety were synthesized and their structures were confirmed by 1H NMR, 13C NMR and elemental analyses. Antiviral bioassays revealed that most of the compounds exhibited good antiviral activity against tobacco mosaic virus (TMV) at a concentration of 500 μg mL-1. The designated compound 4l was 50% effective in terms of curative and protective activities against TMV with 50% effective concentrations (EC50) of 10.9 and 79.4 μg mL-1, which were better than those of ningnanmycin (81.4 and 82.2 μg mL-1). Microscale thermophoresis (MST) also showed that the binding of compound 4l to coat protein (TMV-CP) yielded a Kd value of 0.275 ± 0.160 μmol L-1, which was better than that of ningnanmycin (0.523 ± 0.250 μmol L-1). At the same time, molecular docking studies for 4l with TMV-CP (PDB code:1EI7) showed that the compound was embedded well in the pocket between the two subunits of TMV-CP. Meanwhile, compound 4a demonstrated excellent antibacterial activities against Ralstonia solanacearum (R. solanacearum), with an EC50 value of 0.1 μg mL-1, which was better than that of thiodiazole-copper (36.1 μg mL-1) and bismerthiazol (49.5 μg mL-1). The compounds act by causing folding and deformation of the bacterial cell membrane as observed using scanning electron microscopy (SEM). The chalcone derivatives thus synthesized could become potential alternative templates for novel antiviral and antibacterial agents.
- Tang, Xu,Su, Shijun,Chen, Mei,He, Jun,Xia, Rongjiao,Guo, Tao,Chen, Ying,Zhang, Cheng,Wang, Jun,Xue, Wei
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p. 6011 - 6020
(2019/03/12)
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- Synthesis and antibacterial evaluation of novel chalcone derivatives containing a benzothiazole scaffold
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Abstract: A series of novel chalcone derivatives containing a benzothiazole scaffold were synthesized to develop novel antibacterial agents for solving the problem of drug resistance. Most compounds exhibited excellent antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), and Ralstonia solanacearum (Rs) compared to a reference drug, bismerthiazol. The results indicated that chalcone derivatives containing a benzothiazole scaffold merit more research as promising antibacterial agents. Graphical abstract: [Figure not available: see fulltext.].
- Wang, Yihui,Li, Pu,Jiang, Shichun,Chen, Ying,Su, Shijun,He, Jun,Chen, Mei,Zhang, Juping,Xu, Weiming,He, Ming,Xue, Wei
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- Discovery of novel human inosine 5′-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents
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The enzyme inosine 5′-monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotides, and thus regulates the guanine nucleotide pool required for cell proliferation. Of the two isoforms, human IMPDH type 2 (hIMPDH2) is a validated molecular target for potential immunosuppressive, antiviral and anticancer chemotherapy. In search of newer hIMPDH2 inhibitors as potential anticancer agents, three novel series (A: 5-aminoisobenzofuran-1(3H)-one, B: 3,4-dimethoxyaniline and C: benzo[d]-[1,3]dioxol-5-ylmethanamine) were synthesized and evaluated for in vitro and cell-based activities. A total of 37 molecules (29–65) were screened for their in vitro hIMPDH2 inhibition, with particular emphasis on establishing their structure–activity relationship (SAR) trends. Eight compounds (hits, 30, 31, 33–35, 37, 41 and 43) demonstrated significant enzyme inhibition (>70% @ 10 μM); especially the A series molecules were more potent than B series (50 values for the hits ranged from 0.36 to 7.38 μM. The hits displaying >80% hIMPDH2 inhibition (30, 33, 35, 41 and 43) were further assessed for their cytotoxic activity against cancer cell lines such as MDA-MB-231 (breast adenocarcinoma), DU145 (prostate carcinoma), U87 MG (glioblastoma astrocytoma) and a normal cell line, NIH-3T3 (mouse embryonic fibroblast) using MTT assay. Most of the compounds exhibited higher cellular potency against cancer cell lines and notably lower toxicity towards NIH-3T3 cells compared to mycophenolic acid (MPA), a prototypical hIMPDH2 inhibitor. Two of the series A hits (30 and 35) were evaluated in human peripheral blood mononuclear cells (hPBMC) assay and found to be better tolerated than MPA. The calculated/predicted molecular and physicochemical properties were satisfactory with reference to drug-likeness. The molecular docking studies clearly demonstrated crucial interactions of the hits with the cofactor-binding site of hIMPDH2, further providing critical information for refining the design strategy. The present study reports the design and discovery of structurally novel hIMPDH2 inhibitors as potential anticancer agents and provides a guide for further research on the development of safe and effective anticancer agents, especially against glioblastoma.
- Shah, Chetan P.,Kharkar, Prashant S.
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p. 286 - 301
(2018/09/18)
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- Pyridine-containing benzothiazepine derivatives, and preparation method and application thereof
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The invention discloses pyridine-containing benzothiazepine derivatives, and a preparation method and application thereof. The general formula (I) of the derivatives is described in the specification. In the formula (I), R is selected from a group consisting of a phenyl group, a 4-methylphenyl group, a thien-2-yl gourp, a 4-methoxyphenyl group, a 4-nitrophenyl group, a 4-trifluoromethoxyphenyl group, a 4-bromophenyl group, a furan-2-yl group, a 4-fluorophenyl group, a 3,4-dimethyoxyphenyl group, a 2-chlorophenyl group, a 2-phenyl group, a 3-bromophenyl group, a 2-methyoxyphenyl group, a 2-fluorophenyl group, a 3-methyoxyphenyl group, a 4-trifluoromethylphenyl group, a 2-trifluoromethylphenyl group, a 4-chlorophenyl group, a 3-fluorophenyl group, a 2,4-dichlorophenyl group, a 3,4-dichlorophenyl group, a 2,6-dichlorophenyl group, a 2-chloro-6-fluorophenyl group, a 3-nitrophenyl group and a naphtha-1-yl group. According to the invention, synthesis route is simple; yield is high; and plant virus diseases can be efficiently and safely prevented and controlled.
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Paragraph 0015; 0035
(2016/10/10)
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- Synthesis and biological evaluation of oleanolic acid derivative-chalcone conjugates as α-glucosidase inhibitors
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α-Glucosidase is a promising target for the treatment of obesity and diabetes mellitus. A series of oleanolic acid derivative-chalcone conjugates were designed and synthesized as α-glucosidase inhibitors. Their structures were determined by spectroscopic analysis and their α-glucosidase inhibitory activities were investigated in vitro. Most conjugates exhibited moderate inhibitory activity against α-glucosidase; among them, conjugate 1b (IC50 = 3.2 ± 0.2 μM) possessed the strongest α-glucosidase inhibitory activity, and the preliminary structure-activity relationship showed that the furan or thiophene rings in the chalcone units of the conjugates had a tendency to enhance the activity. Lineweaver-Burk plot analysis demonstrated competitive inhibition of α-glucosidase activity by 1b, 6b, 5c and 4d; their inhibition constant (Ki) values were 16.6, 29.3, 14.6 and 20.6 μM, respectively. The interaction forces between the conjugates and α-glucosidase were hydrogen bonding and van der Waals.
- Tang, Chu,Zhu, Linhui,Chen, Yu,Qin, Rui,Mei, Zhinan,Xu, Jing,Yang, Guangzhong
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p. 10862 - 10874
(2014/03/21)
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- Design, synthesis and antitumor activity of novel artemisinin derivatives using hybrid approach
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In an attempt to develop potent and selective anti-tumor agents, two novel series of artemisinin-chalcone hybrids were designed, synthesized and screened for their antitumor activities against HT-29, A549, MDA-MB-231, HeLa and H460 cell lines in vitro. Nearly all of the tested compounds showed significantly increased anti-tumor activity compared with the corresponding dihydroartemisinin (DHA). Most of the title compounds displayed good selectivity toward HT-29 and HeLa cell lines with IC50 values ranging from 0.09 to 0.85μM. Among them, the most promising compound 9c (IC50 range of 0.09-0.93μM) was 10.5- to 70-times more active than DHA (IC50 range of 5.6-15.6μM) respectively.
- Xie, Lijun,Zhai, Xin,Ren, Lixiang,Meng, Haiyan,Liu, Chun,Zhu, Wufu,Zhao, Yanfang
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experimental part
p. 984 - 990
(2011/10/09)
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- Screening of biological activities of a series of chalcone derivatives against human pathogenic microorganisms
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In an effort to develop new antimicrobial agents, a series of chalcone derivatives, 3-60, were prepared by Claisen-Schmidt condensation of appropriate acetophenones and 2-furyl methyl ketones with appropriate aromatic aldehydes, furfural, and thiophene-2-carbaldehyde in an aqueous solution of NaOH and EtOH at room temperature. The synthesized compounds were characterized by means of their IR- and NMR-spectral data, and elemental analysis. All compounds were tested for their antibacterial and antifungal activities by the disc diffusion method. For the most active compounds, also minimum inhibitory concentrations (MICs) were determined.
- Karaman, Isa,Gezegen, Hayreddin,Guerdere, M. Burcu,Dingil, Alparslan,Ceylan, Mustafa
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experimental part
p. 400 - 408
(2010/09/04)
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- Synthesis and fungicidal evaluation of novel chalcone-based strobilurin analogues
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Strobilurin derivatives have become one of the most important classes of agricultural fungicide due to a novel action mode, wide fungicidal spectrum, lower toxicity toward mammalian cells, and environmentally benign characteristics. To discover new strobilurin analogues with high activity against resistant pathogens, a series of new chalcone-based strobilurin derivatives are designed and synthesized by integrating a chalcone scaffold with a strobilurin pharmacophore. The preliminary bioassay showed that some of the chalcone analogues exhibited good in vivo fungicidal activities against Pseudoperoniospora cubensis and Sphaerotheca fuliginea at the dosage of 200 μg mL-1. Two compounds, (£)-methyl 2-[2-({3-[(£)-3-(2- chlorophenyl)acryloyl]phenoxy}methyl)phenyl]-3-meth-oxyacrylate (1e) and (E)-methyl 2-[2-({3-[(E)-3-(3-bromophenyl)acryloyl]phenoxy}methyl)phenyl]-3- methoxyacrylate (11), were found to display higher fungicidal activities against P. cubensis (EC90 = 118.52 μg ml-1 for 1e and EC 90 = 113.64 μg mL-1 for 11) than Kresoxim-methyl (EC90 = 154.92 μg mL-1) and were identified as the most promising candidates for further study. The present work demonstrated that strobilurin analogues containing chalcone as a side chain could be used as a lead structure for further developing novel fungicides. To our knowledge, this is the first report about the syntheses and fungicidal activities of chalcone-based strobilurin derivatives.
- Zhao, Pei-Liang,Liu, Chang-Ling,Huang, Wei,Wang, Ya-Zhou,Yang, Guang-Fu
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p. 5697 - 5700
(2008/03/14)
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- Phosphate transport inhibitors
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Disclosed are compounds which have been identified as inhibitors of phosphate transport. Many of the compounds are represented by Structural Formula (I): Ar1—W—X—Y—Ar2; or a pharmaceutically acceptable salt thereof. Ar1 and Ar2 are independently a substituted or unsubstituted aryl group or an optionally substituted five membered or six membered non-aromatic heterocylic group fused to an optionally substituted monocylic aryl group. W and Y are independently a covalent bond or a C1-C3 substituted or unsubstituted alkylene group. X is a heteroatom-containing functional group, an aromatic heterocyclic group, substituted aromatic heterocyclic group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, an olefin group or a substituted olefin group. Also disclosed are methods of treating a subject with a disease associated with hyperphosphatemia, as well as a disease mediated by phosphate-transport function. The methods comprise the step of administering an effective amount of the one of the compounds described above.
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- Synthesis and bioefficacy evaluation of 2-[4-(3-arylprop-2-enoyl)phenoxy]-N-substituted acetamides and 2-[4-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-phenoxy]acetic acid hydrazides as potential pesticides
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Base catalyzed condensation of 4-hydroxyacetophenone I with araldehydes 2-8 yields 3-aryl-1-(4-hydroxyphenyl)prop-2-eh-1-ones 9-15, The compounds 9-15 are alkylated with ethyl chloroacetate to furnish ethyl [4-(3-arylprop-2-enoyl)phenoxy]acetates 16-22. The esters 16-22 are subjected to nucleophilic displacement reactions with isopropylamine and morpholine to give the title compounds, 2-[4(-3-arylprop-2-enoyl)phenoxy]-N-isopropylacetamides 23-29 and 4-[{4-(3-arylprop-2-enoyl)phenoxy}acetyl]morpholine 30-36, respectively. The esters 16-22 are cyclized with excess of hydrazine hydrate in ethanol to give the title compounds, 2-[4-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)phenoxy]acetic acid hydrazides 37-43. All the compounds are tested for their toxicity against five phytopathogenic fungi, Rhizoctonia solani, Rhizoctonia bataticola, Sclerotinia sclerotiorum, Alternaria brassicae, and Fusarium solani, two saprophytic fungi Penicillium digitatum, and Aspergillus niger and one phytopathogenic bacterium Xanthomonas campestris pv. citrii. Some of the compounds inhibit the growth of S. sclerotiorum, A. niger and X. campestris pv. citrii at a concentration of 200 ppm.
- Malik,Dahiya,Kumar,Sangwan,Mehta,Sangwa
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p. 682 - 687
(2007/10/03)
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