1076-38-6Relevant articles and documents
Design, synthesis and biological evaluation of novel coumarin-based hydroxamate derivatives as histone deacetylase (HDAC) inhibitors with antitumor activities
Yang, Feifei,Zhao, Na,Song, Jiali,Zhu, Kongkai,Jiang, Cheng-shi,Shan, Peipei,Zhang, Hua
, (2019)
A series of novel coumarin-based hydroxamate derivatives were designed and synthesized as histone deacetylase inhibitors (HDACis). Selective compounds showed a potent HDAC inhibition with nM IC50 values, with the best compound (10e) being nearly 90 times more active than vorinostat (SAHA) against HDAC1. Compounds 10e and 11d also increased the levels of acetylated histone H3 and H4, which is consistent with their strong HDAC inhibition. In addition, 10e and 11d displayed a higher potency toward human A549 and Hela cancer cell lines compared with SAHA. Moreover, 10e and 11d significantly arrested A549 cells at the G2/M phase and enhanced apoptosis. Molecular docking studies revealed the possible mode of interaction of compounds 10e and 12a with HDAC1. Our findings suggest that these novel coumarin-based HDAC inhibitors provide a promising scaffold for the development of new potential cancer chemotherapies.
Coumarin derivatives as potential inhibitors of acetylcholinesterase: Synthesis, molecular docking and biological studies
Singla, Shaffali,Piplani, Poonam
, p. 4587 - 4599 (2016)
A series of novel hybrids has been synthesized by linking coumarin moiety through an appropriate spacer to various substituted heterocyclic amines and evaluated as dual binding site acetylcholinesterase inhibitors for the treatment of cognitive dysfunction caused by increased hydrolysis of acetylcholine and scopolamine induced oxidative stress. Anti-amnesic activity of the compounds was evaluated using Morris water maze model at a dose of 1?mg/kg with reference to the standard, donepezil. Biochemical estimation of oxidative stress markers (lipid peroxidation, superoxide dismutase, and plasma nitrite) was carried out to assess the antioxidant potential of the synthesized molecules. Among all the synthesized compounds (15a–i, 16a–d, 17a–b), compound 15a [4-[3-(4-phenylpiperazin-1-yl)propoxy]-2H-chromen-2-one] displayed significant antiamnesic activity, AChE inhibitory activity (IC50?=?2.42?μM) and antioxidant activity in comparison to donepezil (IC50?=?1.82?μM). Molecular docking study of 15a indicated that it interacts with all the crucial amino acids present at the CAS, mid-gorge and PAS of TcAChE resulting in increased inhibition of AChE enzyme.
Cu (I) Catalyzed One Pot SN-Click Reactions of Halogenated Coumarins and 1-aza-coumarins
Revankar, Hrishikesh M.,Kulkarni, Manohar V.
, p. 537 - 544 (2018)
A one pot three component, copper catalyzed azide-alkyne cycloaddition reaction has been employed for the synthesis of bis-coumarinyl triazoles (A–D) using 4-chloro, 4-bromomethyl, 3-bromoacetyl and 4-bromomethyl-1-aza-coumarins (I–IV), sodium azide, and coumarin propargyl ethers (V–IX) in moderate yields.
A convenient one-pot synthesis of 4-hydroxycoumarin, 4-hydroxythiocoumarin, and 4-hydroxyquinolin-2(1H)-one
Jung,Jung,Park
, p. 1195 - 1200 (2001)
An improved one-pot synthesis of 4-hydroxycoumarin, 4-hydroxythiocoumarin, and 4-hydroxyquinolin-2(1H)-one from 2-hydroxyacetophenone, 2-mercaptoacetophenone, and 2-aminoacetophenone, respectively, is described. The synthetic strategies involve the acylation and internal ring cyclization. This method is readily amenable to large-scale synthesis of 4-hydroxycoumarin, 4-hydroxythiocoumarin, and 4-hydroxyquinolin-2(1H)-one derivatives in high yields.
Synthesis of substituted 4-(4-((3-Nitro-2-oxo-2H-chromene-4-yl)amino)phenyl)morpholine-3-one coumarin derivatives
Sanghani, Yogesh J.,Koradiya, Suresh B.,Patel, Anilkumar S.
, p. 1461 - 1464 (2019)
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.
Synthesis and photooxygenation of furo[3,2-c]coumarin derivatives as antibacterial and DNA intercalating agent
Al-Sehemi, Abdullah G.,El-Gogary, Sameh R.
, p. 316 - 320 (2012)
Syntheses of 2,3-dimethyl-4H-furo[3,2-c]coumarin and 3-phenyl-4H-furo[3,2- c]coumarin as angular furocoumarins were carried out through Williamson reaction of 4-hydroxycoumarin with α-haloketones followed by cyclization. Photooxygenation of the synthesized furocoumarin derivatives was performed and the photoproducts were isolated and characterized. The affinity of 2,3-dimethyl-4H-furo[3,2-c]coumarin towards DNA and the antibacterial activity were evaluated and compared with 8-methoxypsoralen (8-MOP). Syntheses of 2,3-dimethyl-4H-furo[3,2-c]coumarin and 3-phenyl-4H-furo[3,2-c]coumarin as angular furocoumarins were carried out through Williamson reaction of 4-hydroxycoumarin with α-haloketones followed by cyclization. Photooxygenation of the synthesized furocoumarin derivatives was performed and the photoproducts were isolated and characterized. The affinity of 2,3-dimethyl-4H-furo[3,2-c]coumarin towards DNA and the antibacterial activity were evaluated and compared with 8-methoxypsoralen (8-MOP). Copyright
Synthesis and biological evaluation of 4 arylcoumarin analogues as tubulin-targeting antitumor agents
Mutai, Peggoty,Breuzard, Gilles,Pagano, Alessandra,Allegro, Diane,Peyrot, Vincent,Chibale, Kelly
, p. 1652 - 1665 (2017)
The synthesis of twenty-six 4-arylcoumarin analogues of combretastatin A-4 (CA-4) led to the identification of two new compounds (25 and 26) with strong cytotoxic activity. Both compounds had a high cytotoxic effect on a CA-4-resistant colon adenocarcinoma cell line (HT29D4). The compounds affected cell cycle progression characterized by a mitotic block. The activity of these compounds against microtubules both in vitro and in cells was examined and both compounds were found to potently inhibit in vitro microtubule formation via a sub-stoichiometric mode like CA-4. By immunofluorescence, it was observed that both compounds induced strong microtubule network disruption. Our results provide a strong experimental basis to develop new potent anti-tubulin molecules targeting CA-4-resistant cancer cells.
Chromenone derivatives as a versatile scaffold with dual mode of inhibition of HIV-1 reverse transcriptase-associated Ribonuclease H function and integrase activity
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
, (2019)
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.
Microwave-assisted synthesis and antifungal activity of novel fused Osthole derivatives
Zhang, Ming-Zhi,Zhang, Rong-Rong,Wang, Jia-Qun,Yu, Xiang,Zhang, Ya-Ling,Wang, Qing-Qing,Zhang, Wei-Hua
, p. 10 - 16 (2016)
Based on the microwave-assisted synthetic protocol developed in our previous work, we have synthesized a series of novel furo[3,2-c]coumarins as fused Osthole derivatives, via the reaction of 4-hydroxycoumarins and β-ketoesters catalyzed by DMAP. All the target compounds were evaluated in?vitro for their antifungal activity against six phytopathogenic fungi, some compounds exhibited potential activity in the primary assays. Especially compounds 6c, 7b, 8b and 8c (shown in Fig.?1) were the most active ones, EC50values of these four compounds against Colletotrichum capsica, Botrytis cinerea and Rhizoctonia solani were further investigated. 6c was identified as the most promising candidate with the EC50value at 0.110?μM against Botrytis cinerea and 0.040?μM against Colletotrichum capsica, respectively, representing better antifungal activity than that of the commonly used fungicide Azoxystrobin.
One-pot two-step synthesis of 3-iodo-4-aryloxy coumarins and their Pd/C-catalyzed annulation to coumestans
Panda, Niranjan,Mattan, Irshad
, p. 7716 - 7725 (2018)
An efficient protocol for the synthesis of various coumestans from the intramolecular annulation of 3-iodo-4-aryloxy coumarins through C-H activation has been developed. When 3-iodo-4-aryloxy coumarins were treated with 10% Pd/C (0.3 mol% Pd) in the presence of sodium acetate, the corresponding coumestans were produced in good to excellent yield. Reusability of the palladium catalyst was investigated in up to three consecutive cycles and it was found that the yield of the reaction was almost unaltered. Sequential iodination and O-arylation of 4-hydroxy coumarins leading to the 3-iodo-4-aryloxy coumarins were also achieved in a one-pot two-step process starting from aryl iodides in high yield. Pivalic acid was revealed to be the most effective additive for the later method to produce 3-iodo-4-phenoxy coumarins. Different functional groups bearing electron-donating as well as withdrawing groups are also tolerant to the reaction conditions.
