- Synthesis, characterization, and anticoagulant activity of new functionalized biscoumarins
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Despite their rarity and structural complexity, natural and synthetic biscoumarins have polarized much attention from investigators particularly due to their characteristic activity as anticoagulant agents. In this work, a panel of twelve functionalized biscoumarins was synthesized in two schematic steps; the first one started by condensing various phenol-based derivatives with malonic acid via a Pechmann-type reaction yielding alkyl-substituted 4-hydroxycoumarins herein symbolized as (E1-E12). The latter compounds were undergone a self-coupling under the influence of methylene iodide to afford the target functionalized biscoumarins, which were symbolized as (EY1-EY12). The potential of the synthesized biscoumarins as anticoagulant applicants was investigated in vivo using rabbit as an animal model. The employed assay was the prothrombin time that was monitored after three and five days of the last oral treatment. The results gathered from this test revealed that the synthesized biscoumarins have a promising anticoagulant activity compared with warfarin as a standard anticoagulant drug, with privileged influence contributed to those substituted at position 7 of the coumarin framework. The authors concluded that the substitution of an alkyl group at that position of the coumarin monomer may intensify the anticoagulant activity of the prepared biscoumarins. Also, this intensity was directly proportionated to the increase in the molecular weight of this alkyl group. Accordingly, the synthesized biscoumarins possessing this property would provide an efficient base for synthesizing new compounds, which have a promising anticoagulant effect.
- Mustafa, Yasser Fakri,Mohammed, Eman Tareq,Khalil, Raghad Riyadh
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p. 4461 - 4468
(2021/08/07)
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- Regioselective Synthesis of 4,5-Dihydro-6H-oxepino[3,2-c]chromene-2,6(3H)-diones through Palladium-Catalyzed Intramolecular Alkoxycarbonylation of 3-Allyl-4-hydroxycoumarins
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Seven-membered ring lactones fused to coumarin scaffolds were obtained via a palladium-catalyzed regioselective intramolecular alkoxycarbonylation under a CO atmosphere. Cyclocarbonylation of 3-allyl-4-hydroxycoumarin derivatives was accessed in the absen
- Sosa, D. Oliver,Almaraz, Karla,Amézquita-Valencia, Manuel
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supporting information
p. 4682 - 4687
(2019/08/01)
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- Design, synthesis, and mechanism of dihydroartemisinin-coumarin hybrids as potential anti-neuroinflammatory agents
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Cancer patients frequently suffer from cancer-related fatigue (CRF), which is a complex syndrome associated with weakness and depressed mood. Neuroinflammation is one of the major inducers of CRF. The aim of this study is to find a potential agent not only on the treatment of cancer, but also for reducing CRF level of cancer patients. In this study, total-thirty new Dihydroartemisinin-Coumarin hybrids (DCH) were designed and synthesized. The in vitro cytotoxicity against cancer cell lines (HT-29, MDA-MB-231, HCT-116, and A549) was evaluated. Simultaneously, we also tested the anti-neuroinflammatory activity of DCH. DCH could inhibit the activated microglia N9 release of NO, TNF-α, and IL-6. The docking analysis was shown that MD-2, the coreceptor of TLR4, might be one of the targets of DCH.
- Yu, Haonan,Hou, Zhuang,Yang, Xiaoguang,Mou, Yanhua,Guo, Chun
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- Synthesis of substituted 4-(4-((3-Nitro-2-oxo-2H-chromene-4-yl)amino)phenyl)morpholine-3-one coumarin derivatives
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A series of novel 4-(4-amino phenyl) morpholine-3-one substituted coumarin derivatives have been prepared by chloramine coupling reaction and were identified. The novel synthetic route involves nucleophilic substitution reaction of 4-chloro-3-nitro-2H-chromene-2- one with 4-(4-amino phenyl)morpholine-3-one. Due to the presence of nitro group in coumarin derivatives make substitution reaction easy and convenient at low temperature. Using DMF as solvent and K2CO3 as base various substituted 4-(4-((3-nitro-2-oxo-2H-chromen- 4-yl)amino)phenyl)morpholine-3-one derivatives (YS-1 to YS-10) can be obtain in good yield and high purity. Structural characterization of all synthesized compound was done by NMR, Mass and IR spectra.
- Sanghani, Yogesh J.,Koradiya, Suresh B.,Patel, Anilkumar S.
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p. 1461 - 1464
(2019/06/11)
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- Chromenone derivatives as a versatile scaffold with dual mode of inhibition of HIV-1 reverse transcriptase-associated Ribonuclease H function and integrase activity
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A number of compounds targeting different processes of the Human Immunodeficiency Virus type 1 (HIV-1) life cycle have been developed in the continuing fight against AIDS. Coumarin-based molecules already proved to act as HIV-1 Protease (PR) or Integrase (IN) inhibitors and also to target HIV-1 reverse transcriptase (RT), blocking the DNA-dependent DNA-polymerase activity or the RNA-dependent DNA-polymerase activity working as common NNRTIs. In the present study, with the aim to exploit a coumarin-based scaffold to achieve the inhibition of multiple viral coded enzymatic functions, novel 4-hydroxy-2H, 5H-pyrano (3, 2-c) chromene–2, 5–dione derivatives were synthesized. The modeling studies calculated the theoretical binding affinity of the synthesized compounds on both HIV-1 IN and RT-associated Ribonuclease H (RNase H) active sites, which was confirmed by biological assays. Our results provide a basis for the identification of dual HIV-1 IN and RT RNase H inhibitors compounds.
- Esposito, Francesca,Ambrosio, Francesca Alessandra,Maleddu, Rita,Costa, Giosuè,Rocca, Roberta,Maccioni, Elias,Catalano, Raffaella,Romeo, Isabella,Eleftheriou, Phaedra,Karia, Denish C.,Tsirides, Petros,Godvani, Nilesh,Pandya, Hetal,Corona, Angela,Alcaro, Stefano,Artese, Anna,Geronikaki, Athina,Tramontano, Enzo
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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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- Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents
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A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the Km of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-Nacetylglucosamine, and the result of the Ki showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 μg/mL to 2 μg/Ml while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational.
- Ji, Qinggang,Ge, Zhiqiang,Ge, Zhixing,Chen, Kaizhi,Wu, Hualong,Liu, Xiaofei,Huang, Yanrong,Yuan, Lvjiang,Yang, Xiaolan,Liao, Fei
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p. 166 - 176
(2015/12/04)
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- Combined Claisen Rearrangement and Oxidative Cyclization as a Route to Hydroxymethyl Dihydrofuran-Annulated Coumarins
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A convenient and simple method for the synthesis of novel 3,4-dihydrofuran-annulated coumarins, 3-(hydroxymethyl)-2H-furo[3,2-c]chromen-4(3H)-ones 5a, 5b, 5c, 5d, 5e, 5f, 5g, by combined Claisen rearrangement and intramolecular regioselective oxidative cyclization of 4-O-allyl coumarin intermediates 3a, 3b, 3c, 3d, 3e, 3f, 3g using inexpensive oxidizing agent m-CPBA is described. The reaction proceeds smoothly by tandem epoxidation/regioselective 5-exo-tet-intramolecular ring opening. The structures of synthesized compounds are established on the basis of spectral data including IR, 1H NMR, and mass and elemental analyses.
- Jayaprakash, Rao Y.,Chakravarthula, Venu
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p. 1014 - 1018
(2015/08/06)
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- An efficient one-pot synthesis of some new 2,4-diaryl pyrido[3,2-c] coumarins as potent antimicrobial agents
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(Chemical Equation Presented) Poly(ethylene glycol) (PEG-400) has been used as sustainable, nonvolatile, and environmental friendly reaction solvent for the synthesis of title compounds. Various diaryl pyrido[3,2-c]coumarins have been synthesized in one s
- Dawane, Bhaskar S.,Konda, Shankaraiah G.,Bodade, Ragini G.,Bhosale, Raghunath B.
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body text
p. 237 - 241
(2010/04/24)
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- Novel pharmaceutical compounds
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The instant invention provides compounds of Formula I which are leukotriene biosynthesis inhibitors. Compounds of Formula I are useful as anti-atherosclerotic, anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.
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Page/Page column 18
(2008/12/07)
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- THIADIAZOLE SUBSTITUTED COUMARIN DERIVATIVES AND THEIR USE AS LEUKOTRIENE BIOSYNTHESIS INHIBITOR
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The instant invention provides compounds of Formula (Ia) which are leukotriene biosynthesis inhibitors, wherein X is O or S, Y is O, S, -NR6-CHR7- or -NR8-C(O)- and A is selected from 5-membered aromatic heterocyclic ring, 6-membered aromatic heterocyclic ring, naphthelenic or heterobicyclic aromatic ring system, phenyl and benzyl. A is optionally mono- or disubstituted. Compounds of Formula (Ia) are useful as anti-atherosclerotic, anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.
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Page/Page column 29-30
(2008/06/13)
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- Bis (biaryl) compounds as inhibitors of leukotriene biosynthesis
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Compounds having the Formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection and in preventing the formation of atherosclerotic plaques.
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