- Synthesis and complementary complex formation properties of oligonucleotides covalently linked to new stabilizing agents
-
Oligodeoxyribonucleotides of different lengths have been prepared and linked to new stabilizing agents related to the coumarin family. These ODNSAs (OligoDeoxyriboNucleotides with Stabilizing Agents) were tested against acridine connected oligomers of the same sequence. Melting temperature experiments demonstrated that all ODNSAs formed complexes of increased stability with complementary sequences of deoxyribo-20-mer. The order of stability of duplexes showed that the coumarins stabilize the complexes more than the acridine and the chromone derivatives.
- Balbi,Balbi, Alessandro,Sottofattori,Sottofattori, Enzo,Grandi,Grandi, Teresa,Mazzei,Mazzei, Mauro,Abramova,Abramova, Tatyana V.,Lokhov,Lokhov, Sergej G.,Lebedev,Lebedev, Alexander V.
-
-
Read Online
- Synthesis, structural characterization, and molecular docking study of new phthalhydrazide-coumarin hybrids
-
A series of new phthalhydrazide-coumarin hybrids was obtained in the reaction of phthalhydrazide with corresponding bromopropoxycoumarin derivatives. These reactions were performed in the presence of Cs2CO3, in acetonitrile as solvent, and under reflux for 5 h. Obtained hybrids contain one or two coumarin scaffolds bonded to phthalhydrazide nitrogen via propoxy linker. Ten new phthalhydrazide-coumarin hybrids were obtained in moderate to good yields, and characterized with melting point, elemental analysis, IR and NMR spectroscopy, and LC-MS spectrometry. Additionally, the structures of these compounds were elucidated based on experimental and theoretical data (IR, 1H NMR, and 13C NMR). Excellent agreement between experimental and simulated spectra was achieved. The prediction of the potential biological activity of synthesized compounds was done using the online program PASS (Prediction of Activity Spectra for Substances). Based on the obtained results, the serotonin 2A receptor (5-HT2AR) was selected for molecular docking study. Molecular docking was also performed with commercially available drug Risperidone, and obtained results were compared with potential bioactive conformations of obtained phthalhydrazide-coumarin hybrids.
- Litinas, Konstantinos E.,Petrovi?, Vladimir P.,Petrovi?, Zorica D.,Simijonovi?, Du?ica,Vlachou, Evangelia-Eirini N.
-
-
Read Online
- A highly selective colorimetric and fluorescent chemosensor for Cr2+in aqueous solutions
-
A new rhodamine-based chemosensor was synthetized through a modified copper-catalyzed [3+2]-cycloaddition of an azidocoumarin with an alkynyl-rhodamine. Its sensing properties toward various metal cations in aqueous solutions were investigated by colorimetric changes, UV–vis and fluorescence spectroscopies. The sensor exhibited a high selectivity for Cr2+over Cr3+and other divalent cations such as Cu2+, Mg2+, Zn2+, Ca2+, Cd2+, Co2+, Hg2+and Ni2+. The linear range of detection by fluorescence spectroscopy is 0.07–3.5?mM, with a detection limit of ca. 64?μM. The binding mode of Cr2+with the sensor was rationalized through experimental evidences.
- Rull-Barrull,d'Halluin,Le Grognec,Felpin
-
-
Read Online
- Synthesis and biological evaluation of novel coumarin derivatives in rhabdoviral clearance
-
Diseases caused by rhabdoviruses have had a huge impact on the productive lives of the entire human population. The main problem is the lack of drugs for the treatment of this family of viruses. Infectious hematopoietic necrosis virus (IHNV), the causative agent of IHN, is a typical rhabdovirus which has caused huge losses to the salmonid industry. Therefore, in this study, IHNV was studied as a model to evaluate the antiviral activity of 35 novel coumarin derivatives. Coumarin A9 was specifically selected for further validation studies upon comparing the half maximum inhibitory concentration (IC50) of four screened candidate derivatives in epithelioma papulosum cyprinid (EPC) cells, as it exhibited an IC50 value of 2.96 μM against IHNV. The data revealed that A9 treatment significantly suppressed the virus-induced cytopathic effect (CPE) in EPC cells. In addition, A9 showed IC50 values of 1.68 and 2.12 μM for two other rhabdoviruses, spring viremia of carp virus and micropterus salmoides rhabdovirus, respectively. Furthermore, our results suggest that A9 exerts antiviral activity, but not by destroying the virus particles and interfering with the adsorption of IHNV. Moreover, we found that A9 had an inhibitory effect on IHNV-induced apoptosis in EPC cells, as reflected by the protection against cell swelling, formation of apoptotic bodies, and loss of cell morphology and nuclear division. There was a 19.05 % reduction in the number of apoptotic cells in the A9 treatment group compared with that in the IHNV group. In addition, enzyme activity assays proved that A9 suppressed the expression of caspase 3, 8 and 9. These results suggested that A9 inhibit viral replication, to some extent, by blocking IHNV-induced apoptosis. In an in vivo study, A9 exhibited an anti-rhabdovirus effect in virus-infected fish by substantially enhancing the survival rate. Consistent with the above results, A9 repressed IHNV gene expression in virus-sensitive tissues (brain, kidney and spleen) in the early stages of virus infection. Importantly, the data showed that horizontal transmission of IHNV was reduced by A9 in a static cohabitation challenge model, especially in fish that underwent bath treatment, suggesting that A9 might be a suitable therapeutic agent for IHNV in aquaculture. Therefore, coumarin derivatives can be developed as antiviral agents against rhabdoviruses.
- Chen, Jiong,Hu, Yang,Liu, Lei,Qiu, Tianxiu,Shan, Lipeng
-
supporting information
(2021/08/10)
-
- Synthesis of N-substituted indole derivatives as potential antimicrobial and antileishmanial agents
-
Leishmaniasis and microbial infections are two of the major contributors to global mortality and morbidity rates. Hence, development of novel, effective and safer antileishmanial and antimicrobial agents having reduced side effects are major priority for researchers. Two series of N-substituted indole derivatives i.e. N-substituted indole based chalcones (12a-g) and N-substituted indole based hydrazide-hydrazones (18a-g, 19a-f, 21 a-g) were synthesized. The synthesized compounds were characterized by 1H NMR, 13C NMR, Mass and FT-IR spectral data. Further these derivatives were evaluated for their antimicrobial potential against Escherichia coli, Bacillus subtilis, Pseudomonas putida and Candida viswanathii, and antileishmanial potential against promastigotes of Leishmania donovani. Compounds 18b, 18d and 19d exhibited significant activity with an IC50 of 0.19 ± 0.03 μM, 0.14 ± 0.02 μM and 0.16 ± 0.06 μM against B. subtilis which was comparable to chloramphenicol (IC50 of 0.25 ± 0.03 μM). Compounds 12b and 12c exhibited an IC50 of 24.2 ± 3.5 μM and 21.5 ± 2.1 μM in the antileishmanial assay. Binding interactions of indole based hydrazide-hydrazones were studied with nitric oxide synthase in silico in order to understand the structural features responsible for activity.
- Banerjee, Uttam Chand,Bharatam, Prasad V.,Kirar, Seema,Neerupudi, Kishore Babu,Singh, Inder Pal,Singh, Sushma,Tiwari, Shweta,Wani, Aabid Abdullah
-
-
- New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation
-
A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with mixed type inhibition scenario. Structure-activity relationship revealed that three-carbon alkyl chain connecting coumarin and triazole is well tolerable for inhibitory potential. Hybrids obtained from 4-hydroxycoumarin and 1-benzotriazole were most potent AChE inhibitors. The inhibitory potential of all compounds against butyrylcholinesterase was also evaluated but all showed negligible activity suggesting that the hybrid molecules are selective AChE inhibitors. 13b (most potent AChE inhibitor) also showed copper-induced Aβ1-42 aggregation inhibition (34.26% at 50 μΜ) and chelating properties for metal ions (Cu2+, Fe2+, and Zn2+) involved in AD pathogenesis along with DNA protective potential against degenerative actions of [rad]OH radicals. Molecular modelling studies confirm the potential of 13b in blocking both PAS and CAS of AChE. In addition, interactions of 13b with Aβ1-42 monomer are also streamlined. Therefore, hybrid 13b can act as an effective hit lead molecule for further development of selective AChE inhibitors as multifunctional anti-Alzheimer's agents.
- Arora, Saroj,Attri, Shivani,Bhagat, Kavita,Kaur Gulati, Harmandeep,Kaur, Prabhjot,Kumar, Nitish,Mohinder Singh Bedi, Preet,Sharma, Sahil,Singh, Atamjit,Singh, Harbinder,Vir Singh, Jatinder
-
-
- Synthesis, biological activity and multiscale molecular modeling studies of bis-coumarins as selective carbonic anhydrase IX and XII inhibitors with effective cytotoxicity against hepatocellular carcinoma
-
A series of novel bis-coumarin derivatives containing triazole moiety as a linker between the alkyl chains was synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms I, II, IX and XII were evaluated. In addition, cytotoxic effects of the synthesized compounds on renal adenocarcinoma (769P), hepatocellular carcinoma (HepG2) and breast adeno carcinoma (MDA-MB-231) cell lines were examined. While the hCA I and II isoforms were inhibited in the micromolar range, the tumor-associated isoform hCA IX and XII were inhibited in the high nanomolar range. 4-methyl-7-((1-(12-((2-oxo-2H-chromen-7-yl)oxy)dodecyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (5p) showed the strongest inhibitory activity against hCA IX with the Ki of 144.6 nM and 4-methyl-7-((1-(10-((2-oxo-2H-chromen-7-yl)oxy)decyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (5n) exhibited the highest hCA XII inhibition with the Ki of 71.5 nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modelling approaches were applied. Low energy docking poses of studied molecules at the binding sites of targets have been predicted. In addition, electrostatic potential surfaces (ESP) for binding sites were also generated to understand interactions between proteins and active ligands.
- Kurt, Belma Zengin,Dag, Aydan,Do?an, Berna,Durdagi, Serdar,Angeli, Andrea,Nocentini, Alessio,Supuran, Claudiu T.,Sonmez, Fatih
-
p. 838 - 850
(2019/04/25)
-
- Synthesis and antiviral activity of coumarin derivatives against infectious hematopoietic necrosis virus
-
Infectious hematopoietic necrosis virus (IHNV)is a highly contagious disease of juvenile salmonid species. However, robust anti-IHNV drugs currently are extremely scarce. For the purpose of seeking out anti-IHNV drugs, here a total of 24 coumarin derivatives are designed, synthesized and evaluated for their anti-viral activities. By comparing the half maximal inhibitory concentrations (IC50)of the 12 screened candidate drugs in epithelioma papulosum cyprini (EPC)cells infected with IHNV, the imidazole coumarin derivative C4 is selected for additional validation studies, with an IC50 of 2.53 μM at 72 h on IHNV glycoprotein. Further experiments revealed that C4 could significantly inhibit apoptosis and cellular morphological damage induced by IHNV. On account of these findings, derivative C4 could be a viable way of controlling IHNV and considered as a promising lead compound for the development of commercial drugs.
- Hu, Yang,Chen, Weichao,Shen, Yufeng,Zhu, Bin,Wang, Gao-Xue
-
supporting information
p. 1749 - 1755
(2019/05/21)
-
- Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells
-
Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy ba
- Yao, Jian-Ning,Zhang, Xue-Xiu,Zhang, Yan-Zhen,Li, Jia-Heng,Zhao, Dong-Yao,Gao, Bing,Zhou, Hai-Ning,Gao, Shi-Lin,Zhang, Lian-Feng
-
p. 1300 - 1308
(2019/04/25)
-
- Novel tacrine-coumarin hybrids linked to 1,2,3-triazole as anti-Alzheimer's compounds: In vitro and in vivo biological evaluation and docking study
-
A new series of tacrine-coumarin hybrids linked to 1,2,3-triazole were designed, synthesized, and tested as potent dual binding site cholinesterase inhibitors (ChEIs) for the treatment of Alzheimer's disease (AD). Among them, compound 8e was the most potent anti-AChE derivative (IC50 = 27 nM) and compound 8m displayed the best anti-BChE activity (IC50 = 6 nM) much more active than tacrine and donepezil as the reference drugs. Compound 8e was also evaluated for its BACE1 inhibitory activity and neuroprotectivity against PC12 cells exposed to Aβ25-35 which indicated low activity. Finally, in vivo studies by Morris water maze task showed that compound 8e significantly reversed scopolamine-induced memory deficit in rats.
- Najafi, Zahra,Mahdavi, Mohammad,Saeedi, Mina,Karimpour-Razkenari, Elahe,Edraki, Najmeh,Sharifzadeh, Mohammad,Khanavi, Mahnaz,Akbarzadeh, Tahmineh
-
p. 303 - 316
(2018/11/10)
-
- Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant
-
A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC50 = 20 nM) and selectivity (IC50 BuChE/AChE = 354), quite similar to the reference drug donepezil (IC50 = 6 nM; IC50 BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations.
- de Souza, Gabriela Alves,da Silva, Soraia John,Del Cistia, Catarina de Nigris,Pitasse-Santos, Paulo,Pires, Lucas de Oliveira,Cardoso, Cristiane Martins,Castro, Rosane Nora,Sant’Anna, Carlos Mauricio R.,Kümmerle, Arthur Eugen,Passos, Yulli Moraes,Cordeiro, Yraima
-
p. 631 - 637
(2019/04/16)
-
- Synthesis of coumarin-sulfonamide derivatives and determination of their cytotoxicity, carbonic anhydrase inhibitory and molecular docking studies
-
Carbonic anhydrases isoforms CA IX, and XII are known to be highly expressed in various human tissues and malignancies. CA IX is a prominent target for especially colorectal cancers, because it is overexpressed in colorectal cancer and this overexpression
- Zengin Kurt, Belma,Sonmez, Fatih,Ozturk, Dilek,Akdemir, Atilla,Angeli, Andrea,Supuran, Claudiu T.
-
-
- 1,3,5-triazaspiro[5.5]undeca-2,4-dienes as selective Mycobacterium tuberculosis dihydrofolate reductase inhibitors with potent whole cell activity
-
The emergence of multi- and extensively-drug resistant tubercular (MDR- and XDR-TB) strains of mycobacteria has limited the use of existing therapies, therefore new drugs are needed. Dihydrofolate reductase (DHFR) has recently attracted much attention as
- Yang, Xuan,Wedajo, Wassihun,Yamada, Yoshiyuki,Dahlroth, Sue-Li,Neo, Jason Jun-Long,Dick, Thomas,Chui, Wai-Keung
-
p. 262 - 276
(2017/12/28)
-
- Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds
-
A novel series of coumarin-lipoic acid conjugates were synthesized via cycloaddition click reaction to find out new multi-target-directed ligands (MTDLs) for treatment of Alzheimer's disease (AD). All of synthesized compounds were screened for neuroprotec
- Jalili-Baleh, Leili,Forootanfar, Hamid,Kü?ükk?l?n?, Tuba Tüylü,Nadri, Hamid,Abdolahi, Zahra,Ameri, Alieh,Jafari, Mandana,Ayazgok, Beyza,Baeeri, Maryam,Rahimifard, Mahban,Abbas Bukhari, Syed Nasir,Abdollahi, Mohammad,Ganjali, Mohammad Reza,Emami, Saeed,Khoobi, Mehdi,Foroumadi, Alireza
-
p. 600 - 614
(2018/06/26)
-
- Reversible photoreduction of Cu(II)-coumarin metal-organic polyhedra
-
We report a new approach for photoinduced reduction of Cu2+ that will enrich the structural diversity of coordination complexes and be a valuable contributor to the development of Cu+/Cu0-based catalysts. To realize controlled Cu2+ reduction, coumarin as a triplet quencher of excited benzophenone was tethered to Cu(ii)-metal-organic polyhedra (MOPs). The photoinduced catalytic activity of the coumarin-MOPs was also examined in a Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC).
- Bae, Jaeyeon,Baek, Kangkyun,Yuan, Daqiang,Kim, Wooram,Kim, Kimoon,Zhou, Hong-Cai,Park, Jinhee
-
supporting information
p. 9250 - 9253
(2017/08/21)
-
- Design, synthesis and evaluation of coumarin-pargyline hybrids as novel dual inhibitors of monoamine oxidases and amyloid-β aggregation for the treatment of Alzheimer's disease
-
A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-β (Aβ) aggregation and monoamine oxidases
- Yang, Hua-Li,Cai, Pei,Liu, Qiao-Hong,Yang, Xue-Lian,Li, Fan,Wang, Jin,Wu, Jia-Jia,Wang, Xiao-Bing,Kong, Ling-Yi
-
p. 715 - 728
(2017/07/22)
-
- Harnessing the Dual Properties of Thiol-Grafted Cellulose Paper for Click Reactions: A Powerful Reducing Agent and Adsorbent for Cu
-
A new approach exploiting the dual properties of thiol-grafted cellulose paper for promoting copper-catalyzed [3+2]-cycloadditions of organic azides with alkynes and adsorbing residual copper species in solution was developed. The thiol-grafted cellulose
- Rull-Barrull, Jordi,d'Halluin, Martin,Le Grognec, Erwan,Felpin, Fran?ois -Xavier
-
supporting information
p. 13549 - 13552
(2016/10/21)
-
- Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease
-
Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 μM and 0.93 μM, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 μM for hAChE; 1.98 μM for hBuChE; 2.62 μM for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit.
- Xie, Sai-Sai,Lan, Jin-Shuai,Wang, Xiaobing,Wang, Zhi-Min,Jiang, Neng,Li, Fan,Wu, Jia-Jia,Wang, Jin,Kong, Ling-Yi
-
p. 1528 - 1539
(2016/03/16)
-
- Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease
-
A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 11/4M). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment.
- Xie, Sai-Sai,Wang, Xiaobing,Jiang, Neng,Yu, Wenying,Wang, Kelvin D.G.,Lan, Jin-Shuai,Li, Zhong-Rui,Kong, Ling-Yi
-
p. 153 - 165
(2015/03/31)
-
- BENZOPYRONE DERIVATIVE AND USE THEREOF
-
The present invention relates to the field of pharmaceutical chemistry, and in particular, to a benzopyrone derivative and a use thereof. The benzopyrone derivative is compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof. It has been found by experiments that, this type of compounds is useful in prevention or treatment of neuropsychical diseases.
- -
-
Paragraph 0025; 0038; 0040
(2014/03/22)
-
- BENZOPYRONE DERIVATIVE AND USE THEREOF
-
The present invention relates to the field of pharmaceutical chemistry, and in particular, to a benzopyrone derivative and a use thereof. The benzopyrone derivative is compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof. It has been found by experiments that, this type of compounds is useful in prevention or treatment of neuropsychical diseases.
- -
-
Paragraph 0066; 0081; 0089
(2014/05/07)
-
- Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease
-
A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced β-amyloid (Aβ) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 μM) and Aβ aggregation (67.8%, 20 μM). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 μM) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment.
- Xie, Sai-Sai,Wang, Xiao-Bing,Li, Jiang-Yan,Yang, Lei,Kong, Ling-Yi
-
p. 540 - 553
(2013/07/27)
-