- Synthesis of osthole derivatives with grignard reagents and their larvicidal activities on mosquitoes
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The structure of osthole has been modified to improve its larvicidal activity against mosquitoes. A new efficient synthesis of osthole derivatives with Grignard reagents has been developed, which employs CuI and LiCl as promoters and covers a broad range of substrates to afford the corresponding products in mild to good yields (up to 83%). Bio-activity evaluation showed that several products exhibited better activities than osthole. CuI and LiCl promoted efficient synthesis of osthole derivatives with Grignard reagents has been developed. Bio-activity evaluation showed that several products exhibited far better larvicidal activities against mosquitoes than osthole.
- Liu, Ming,Liu, Yang,Hua, Xuewen,Wu, Changchun,Zhou, Sha,Wang, Baolei,Li, Zhengming
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Read Online
- Synthesis and biological evaluation of novel 4,7-dihydroxycoumarin derivatives as anticancer agents
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A series of novel 4,7-dihydroxycoumarin based acryloylcyanohydrazone derivatives were synthesized and evaluated for antiproliferative activity against four different cancer cell lines (A549, HeLa, SKNSH, and MCF7). Most of the compounds displayed potent c
- Govindaiah, Pilli,Dumala, Naresh,Grover, Paramjit,Jaya Prakash
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Read Online
- Synthesis and characterization of some coumarins with two hydroxy or methoxy substituents
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The first synthesis of the 6-hydroxy-4-methoxycoumarin (5) was carried out in 25% overall yield from 6-methoxy-4-hydroxycoumarin (1) by hydrolysis of the methoxy group and subsequent selective methylation of the hydroxyl group at position 4. The 1H and 13C NMR data of compounds 1-6 are reported.
- Fall,Santana,Uriarte
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Read Online
- Synthesis and cytotoxic activities of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(-)-cis-khellactone derivatives that induce apoptosis via the intrinsic pathway
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This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(-)-cis-khellactones. The newly synthesized compounds were characterized by1H nuclear magnetic resonance (NMR),13
- Chen, Jingrun,Liu, Junjie,Cui, Dongxiao,Yan, Chaoqun,Meng, Liqiang,Sun, Liqian,Ban, Shurong,Ge, Rui,Liang, Taigang,Li, Qingshan
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Read Online
- Lysosome-targeted Cys near-infrared fluorescent probe and preparation method and application thereof
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The invention belongs to the technical field of analysis and detection, and provides a lysosome-targeted Cys near-infrared fluorescent probe and a preparation method and application thereof. The near-infrared fluorescent probe is 3-(2-(3-(dicyanomethylene
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Paragraph 0015-0016
(2020/08/22)
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- Design, synthesis, biological and in silico evaluation of coumarin-hydrazone derivatives as tubulin targeted antiproliferative agents
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Coumarin-based different series of hydrazone derivatives were synthesized and evaluated for anticancer activity against four different human cancer cell lines. The activity of the compounds were compared with doxorubicin as a standard drug and all the compounds exhibited good to moderate cytotoxicity with IC50 values ranging from 6.07 to 60.45 μM against all the examined cancer cell lines. Based on the screening results, it was concluded that the compounds 12a and 18a were the most promising medicinal entities. In vitro tubulin polymerisation inhibition assay was performed for the compounds 12a and 18a and these two compounds displayed good potency when compared with colchicine as the standard drug. The interaction of these compounds with tubulin protein was also studied with the help of molecular docking technique using Discovery studio software. Furthermore, the molecular and ADMET properties of the compounds were computed with Osiris property software and PreADMET server. The compounds exhibited exciting in vitro and in silico results. Hence we propose that the compounds 12a and 18a could be developed as tubulin targeted potential antiproliferative agents.
- Govindaiah,Dumala, Naresh,Mattan, Irshad,Grover, Paramjit,Jaya Prakash
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- Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease
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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
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supporting information
p. 153 - 165
(2015/03/31)
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- Defining a minimum pharmacophore for simocyclinone D8 disruption of DNA gyrase binding to DNA
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The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have used a deconstruction-reconstruction approach to prepare analogs of the coumarin subunit of SD8 and evaluated their ability to disrupt binding of the DNA gyrase enzyme to DNA in a surface plasmon resonance assay. This has led to a minimum pharmacophore required for disruption of binding. Springer Science+Business Media 2014.
- Gaskell, Lauren M.,Nguyen, Thuy,Ellis, Keith C.
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p. 3632 - 3643
(2014/08/05)
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- Energy transfer in coumarin-sensitised lanthanide luminescence: Investigation of the nature of the sensitiser and its distance to the lanthanide ion
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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
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p. 15981 - 15994
(2013/09/24)
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- Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease
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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
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p. 540 - 553
(2013/07/27)
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- Rational design, synthesis, biological evaluation, homology and docking studies of coumarin derivatives as α1-adrenoceptor antagonists
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According to a three-point pharmacophore for some uro-selective α1-adrenoceptor (AR) antagonists, a novel class of coumarin (=2H-1-benzopyran-2-one) derivatives have been successfully designed and synthesized with high efficacies for α1/s
- Zhou, Xiang,Chen, Ya-Dong,Wang, Tao,Wang, Xiao-Bing,Kong, Ling-Yi
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experimental part
p. 1052 - 1064
(2012/01/06)
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- Coumarin-Based Bioactive Compounds: Facile Synthesis and Biological Evaluation of Coumarin-Fused 1,4-Thiazepines
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As part of our ongoing studies on the synthesis of bioactive coumarin compounds, we synthesized a series of new coumarin-fused 1,4-thiazepines using a simple method. The biological activity of target compounds along with 3-(2-hydroxybenzylidene)chroman-2,4-dione intermediates was screened by evaluation of their antioxidant and cytotoxic activities. The antioxidant activity was assessed using two methods, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method and ferric reducing antioxidant power (FRAP) assay. 4-Methoxyphenolic compound 5d in thiazepine series showed the most potent scavenging activity, while the 4-bromophenolic derivative 5b was the most efficient compound in FRAP assay. Also, the result of cytotoxic evaluation using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay demonstrated that compound 5b is at least twofold more potent than etoposide against MCF-7, SK-N-MC, and MDA-MB 231 cell lines. A series of new coumarin-fused 1,4-thiazepines were synthesized using a simple method. The biological activities of target compounds were screened by evaluation of their antioxidant and cytotoxic activities.
- Khoobi, Mehdi,Foroumadi, Alireza,Emami, Saeed,Safavi, Maliheh,Dehghan, Gholamreza,Alizadeh, Babak H.,Ramazani, Ali,Ardestani, Sussan K.,Shafiee, Abbas
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experimental part
p. 580 - 586
(2012/05/04)
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- Hydroxycoumarin derivatives: Novel and potent α-glucosidase inhibitors
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A novel class of hydroxycoumarin derivatives were found to be potent α-glucosidase inhibitors. Their syntheses were reported and the structure-activity relationship was established. Kinetic enzymatic assays indicated that compound 10 was a slow-binding and noncompetitive inhibitor with a Ki value of 589 nM, while compound 11 was a competitive inhibitor with a Ki value of 4.810 μM. Among all hydroxycoumarin derivatives studied, compounds 10 and 11 exhibited the highest activities, were specific inhibitors of α-glucosidase, and could be exploited as the lead compounds for the development of potent α-glucosidase inhibitors. Compounds 10 and 11 were also selected for further discussion for the mechanism of enzymatic inhibition.
- Shen, Qiong,Shao, Jialiang,Peng, Quan,Zhang, Wanjin,Ma, Lin,Chan, Albert S. C.,Gu, Lianquan
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experimental part
p. 8252 - 8259
(2011/02/23)
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- Discovery of a novel class of potent coumarin monoamine oxidase B inhibitors: Development and biopharmacological profiling of 7-[(3-chlorobenzyl) oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate (NW-1772) as a highly potent, selective, reversible, and orally active monoamine oxidase B inhibitor
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In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[(m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)-methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.
- Pisani, Leonardo,Muncipinto, Giovanni,Miscioscia, Teresa Fabiola,Nicolotti, Orazio,Leonetti, Francesco,Catto, Marco,Caccia, Carla,Salvati, Patricia,Soto-Otero, Ramon,Mendez-Alvarez, Estefania,Passeleu, Celine,Carotti, Angelo
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experimental part
p. 6685 - 6706
(2010/04/04)
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- Coumarin as attractive Casein Kinase 2 (CK2) inhibitor scaffold: An integrate approach to elucidate the putative binding motif and explain structure-activity relationships
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Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, we have synthetized and tested a small library of coumarins (more than 60), rationalizing the observed structure-activity relationship. Moreover, the most promising inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC), has been also crystallized in complex with CK2, and the experimental binding mode has been used to derive a linear interaction energy (LIE) model.
- Chilin, Adriana,Battistutta, Roberto,Bortolato, Andrea,Cozza, Giorgio,Zanatta, Samuele,Poletto, Giorgia,Mazzorana, Marco,Zagotto, Giuseppe,Uriarte, Eugenio,Guiotto, Adriano,Pinna, Lorenzo A.,Meggio, Flavio,Moro, Stefano
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p. 752 - 759
(2008/09/19)
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- Anti-AIDS agents. 37. Synthesis and structure-activity relationships of (3'R,4'R)-(+)-cis-khellactone derivatives as novel potent anti-HIV agents
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To explore the structural requirements of (+)-cis-khellactone derivatives as novel anti-HIV agents, 24 monosubstituted 3',4'-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK) derivatives were synthesized asymmetrically. These compounds included 4 isomeric monomethoxy analogues (3- 6), 4 isomeric monomethyl analogues (7-10), 4 4-alkyl/aryl-substituted analogues (11-14), and 12 4-methyl-(+)-cis-khellactone derivatives (15-26) with varying 3',4'-substituents. These (+)-cis-khellactone derivatives were screened against HIV-1 replication in acutely infected H9 lymphocytes. The results demonstrated that the (3'R,4'R)-(+)-cis-khellactone skeleton, two (S)-(-)-camphanoyl groups at the 3'- and 4'-positions, and a methyl group on the coumarin ring, except at the 6-position, were optimal structural moieties for anti-HIV activity. 3-Methyl- (7), 4-methyl- (8), and 5-methyl- (9) 3',4'- di-O-(S)-camphanoyl-(3'R,4'R)-(+)-cis-khellactone showed EC50 and therapeutic index values of -5 μM and >2.15 x 106, respectively, in H9 lymphocytes, which are much better than those of DCK and AZT in the same assay. Furthermore, 8 and 9 also showed potent inhibitory activity against HIV-1 replication in the CEM-SS cell line, and most monosubstituted DCK analogues were less toxic than DCK in both assays.
- Xie, Lan,Takeuchi, Yasuo,Cosentino, L. Mark,Lee, Kuo-Hsiung
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p. 2662 - 2672
(2007/10/03)
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- Photoactive coumarin derivatives
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A new class of 3,4-dihydrocoumarin derivatives which are useful as photoactive compounds in a wide variety of applications including photoresists and other opto-electronic applications are disclosed and claimed. Preferred embodiments include ether, ester, carbonate, and sulfonate derivatives of 5-hydroxy, 6-hydroxy, and 7-hydroxy-3-diazo-4-oxo-3,4-dihydrocoumarins. These compounds exhibit very high photosensitivity in the deep ultraviolet (DUV) region (ca. 250 nm), and therefore, are useful as photoactive compounds in DUV photoresist formulations.
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- Process for preparing photoactive coumarin derivatives
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Novel processes for the preparation of a new class of coumarin derivatives, which are useful as photoactive compounds in a wide variety of applications including photoresists and other opto-electronic applications, are disclosed and claimed. The process involves a multi-step synthetic method for the preparation of ether, ester, carbonate, or sulfonate derivative of 5-hydroxy, 6-hydroxy, or 7-hydroxy-3-diazo-4-oxo-3,4-dihydrocoumarin starting from the corresponding dihydroxyacetophenone. The compounds formed from the process of the present invention exhibit very high photosensitivity in the deep ultraviolet (DUV) region (ca. 250 nm), and therefore, are useful as photoactive compounds in DUV photoresist formulations.
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- Anti-AIDS agents - XXVIII. Synthesis and anti-HIV activity of methoxy substitute 3',4'-di-O-(-)-Camphanoyl-(+)-cis-Khellactone (DCK) analogues
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Four isomeric methoxy substituted DCK analogues (3-6) were asymmetrically synthesized from different starting materials. 5-Methoxy-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (5) exhibited extremely potent anti-HIV activity against HIV-1 replication in H9 lymphocyte cells with EC50 and therapeutic index values of 0.00038 μM and >402,632, respectively, which are better than those of DCK and AZT in this assay.
- Takeuchi, Yasuo,Xie, Lan,Cosentino, L. Mark,Lee, Kuo-Hsiung
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p. 2573 - 2578
(2007/10/03)
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- MUSHROOM TYROSINASE CATALYSED SYNTHESIS OF COUMENTANS, BENZOFURAN DERIVATIVES AND RELATED HETEROCYCLIC COMPOUNDS
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Full details of an improved synthesis of coumestan derivatives and their structural analogues, viz., wedelolactone, 11-hydroxy aureol, 11-hydroxy coumestrol along benzofuran derivatives and related heterocyclic systems are reported by coupling of in situ generated o-quinones from catechols catalysed by mushroom tyrosinase with various reatants.
- Pandey, G.,Muralikrishna, C.,Bhalerao, U. T.
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p. 6867 - 6874
(2007/10/02)
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- Facile Synthesis of 4-Hydroxycoumarins by Sulfur-Assisted Carbonylation of 2'-Hydroxyacetophenones with Carbon Monoxide
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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
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p. 257 - 259
(2007/10/02)
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