10387-50-5Relevant articles and documents
Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4
Row,Brown,Stachulski,Lennard
, p. 1604 - 1610 (2006)
A number of furanocoumarins isolated from grapefruit juice have been found to inhibit CYP3A4 activity in vitro. In this study, we have designed and synthesised a range of analogues based on bergamottin to investigate the relationship between chemical stru
Interaction of 7-Alkoxycoumarins with the Aryl Hydrocarbon Receptor
Gargaro, Marco,Epifano, Francesco,Fiorito, Serena,Taddeo, Vito Alessandro,Genovese, Salvatore,Pirro, Matteo,Turco, Antonella,Puccetti, Paolo,Schmidt-Weber, Carsten B.,Fallarino, Francesca
, p. 1939 - 1943 (2017)
The aryl hydrocarbon receptor (AhR) is a transcription factor activated by a vast array of natural and synthetic ligands. It plays a pivotal role in numerous physiological and pathological responses, such as cell proliferation and differentiation, induction of xenobiotic metabolizing enzymes, response to environmental toxins, and several others. In this study, we investigated the ability of some natural compounds (oxyprenylated ferulic acid and umbelliferone derivatives) and their semisynthetic analogues (e.g., differently substituted 7-Alkoxycoumarins) to activate AhR, using a reporter luciferase assay. Among them, we found that 7-isopentenyloxycoumarin was the best AhR activator. Boropinic acid, 7-but-2′-enyloxycoumarin, 7-(2′,2′-dimethyl-n-propyloxy)coumarin, 7-benzyloxycoumarin, and 7-(3′-hydroxymethyl-3′-methylallyloxy)coumarin were also active, although to a lesser extent. All the compounds were also analyzed for their ability to inhibit AhR activation, using a reference ligand, 6-formylindolo[3,2-b]carbazole. Data recorded in the present investigation pointed out the importance of a 3,3-dimethylallyloxy side chain attached to the coumarin ring core as a key moiety for AhR activation.
Novel squalene-hopene cyclase inhibitors derived from hydroxycoumarins and hydroxyacetophenones
Cravotto, Giancarlo,Balliano, Gianni,Tagliapietra, Silvia,Oliaro-Bosso, Simonetta,Nano, Gian Mario
, p. 1171 - 1174 (2004)
Squalene-hopene cyclase (SHC) is a useful model enzyme for predicting molecular interactions with oxidosqualene cyclase (OSC). Structure-activity relationships were investigated for numerous coumarin-derived inhibitors of SHC, and structural simplificatio
Combined molecular modeling and cholinesterase inhibition studies on some natural and semisynthetic O-alkylcoumarin derivatives
Orhan, Ilkay Erdogan,Senol Deniz, F. Sezer,Salmas, Ramin Ekhteiari,Durdagi, Serdar,Epifano, Francesco,Genovese, Salvatore,Fiorito, Serena
, p. 355 - 362 (2019)
Coumarins of synthetic or natural origins are an important chemical class exerting diverse pharmacological activities. In the present study, 26 novel O-alkylcoumarin derivatives were synthesized and have been tested at 100 μM for their in vitro inhibitory potential against acetylcholinesterase (AChE) and butyrlcholinesterase (BChE) targets which are the key enzymes playing role in the pathogenesis of Alzheimer's disease. Among the tested coumarins, none of them could inhibit AChE, whereas 12 of them exerted a marked and selective inhibition against BChE as compared to the reference (galanthamine, IC50 = 46.58 ± 0.91 μM). In fact, 10 of the active coumarins showed higher inhibition (IC50 = 7.01 ± 0.28 μM – 43.31 ± 3.63 μM) than that of galanthamine. The most active ones were revealed to be 7-styryloxycoumarin (IC50 = 7.01 ± 0.28 μM) and 7-isopentenyloxy-4-methylcoumarin (IC50 = 8.18 ± 0.74 μM). In addition to the in vitro tests, MetaCore/MetaDrug binary QSAR models and docking simulations were applied to evaluate the active compounds by ligand-based and target-driven approaches. The predicted pharmacokinetic profiles of the compounds suggested that the compounds reveal lipophilic character and permeate blood brain barrier (BBB) and the ADME models predict higher human serum protein binding percentages (>50%) for the compounds. The calculated docking scores indicated that the coumarins showing remarkable BChE inhibition possessed favorable free binding energies in interacting with the ligand-binding domain of the target. Therefore, our results disclose that O-alkylcoumarins are promising selective inhibitors of cholinesterase enzymes, particularly BChE in our case, which definitely deserve further studies.
Synthesis and biological evaluation of isoprenylated coumarins as potential anti-pancreatic cancer agents
Jun, Maria,Bacay, Alyssa F.,Moyer, James,Webb, Andrew,Carrico-Moniz, Dora
, p. 4654 - 4658 (2014)
A series of isoprenylated coumarins has been designed, synthesized, and evaluated against human pancreatic adenocarcinoma cell line PANC-1 under nutrient-rich and nutrient-deprived conditions. The compounds described investigate the effect of isoprenyl chain length and positioning on cell growth inhibition. The majority of these compounds displayed cytotoxicity against PANC-1 cells selectively in the absence of essential amino acids, glucose, and serum, and showed no cytotoxicity under nutrient-rich conditions. In this study, compound 6 exhibited the highest cytotoxic activity with an LC50value of 4 μM and induced apoptosis-like morphological changes in PANC-1 cells after a 24-h incubation. The evaluated structure-activity relationships show that substitution at the 6-position and the presence of a farnesyl isoprenyl tail are important structural features for enhanced preferential cytotoxicity. These findings provide important information to designing other structural analogues for potential application as novel pancreatic antitumor agents.
Structure-activity relationship of natural and synthetic coumarins inhibiting the multidrug transporter P-glycoprotein
Raad, Imad,Terreux, Raphael,Richomme, Pascal,Matera, Eva-Laure,Dumontet, Charles,Raynaud, Jean,Guilet, David
, p. 6979 - 6987 (2006)
A set of 32 natural and synthetic coumarins were tested in order to evaluate their activity on human leukemic cells (K562/R7) overexpressing P-glycoprotein (P-gp). Their ability to reduce the P-gp-mediated drug efflux of daunorubicin out of cells was eval
Collection of alkenylcoumarin derivatives as Taq DNA polymerase inhibitors: SAR and in silico simulations
Bruna-Haupt, Ezequiel,Garro, Hugo A.,Gutiérrez, Lucas,Pungitore, Carlos R.
, p. 1432 - 1442 (2018)
Using a feasible method, we generated a small focused library of structurally related alkenylcoumarins. These compounds were evaluated as potential antitumoral agents against Taq DNA polymerase. 6-(pent-4-enyloxy)-coumarin (7) IC50 = 48.33 ± 2.85 μM was defined as a small molecule able to disturb DNA replication. Docking and Molecular Dynamic Simulations suggest an active-site binding. Structure/activity relationship was reasonably established. Compound 7 represents a potential structure for further studies in the development of new anti-cancer DNA/polymerase binding agents.
Investigation of the cytotoxicity of bioinspired coumarin analogues towards human breast cancer cells
Gkionis, Leonidas,Kavetsou, Eleni,Kalospyros, Alexandros,Manousakis, Dimitris,Garzon Sanz, Miguel,Butterworth, Sam,Detsi, Anastasia,Tirella, Annalisa
, p. 307 - 321 (2021)
Abstract: Coumarins possess a wide array of therapeutic capabilities, but often with unclear mechanism of action. We tested a small library of 18 coumarin derivatives against human invasive breast ductal carcinoma cells with the capacity of each compound to inhibit cell proliferation scored, and the most potent coumarin analogues selected for further studies. Interestingly, the presence of two prenyloxy groups (5,7-diprenyloxy-4-methyl-coumarin, 4g) or the presence of octyloxy substituent (coumarin 4d) was found to increase the potency of compounds in breast cancer cells, but not against healthy human fibroblasts. The activity of potent compounds on breast cancer cells cultured more similarly to the conditions of the tumour microenvironment was also investigated, and increased toxicity was observed. Results suggest that tested coumarin derivatives could potentially reduce the growth of tumour mass. Moreover, their use as (combination) therapy in cancer treatment might have the potential of causing limited side effects. Graphic abstract: [Figure not available: see fulltext.].
Visible-Light-Induced Direct Csp2-H Radical Trifluoroethylation of Coumarins with 1,1,1-Trifluoro-2-iodoethane (CF3CH2I)
Chen, Xiaoyu,Li, Linlin,Pei, Congcong,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
, p. 2772 - 2783 (2021/02/27)
Herein, we developed the first visible-light-induced direct Csp2-H radical 2,2,2-trifluoroethylation of coumarins with commercially available and cheap reagent CF3CH2I at room temperature. This transformation proceeded smoothly under mild conditions and showed excellent functional group compatibility. The synthetic value of the protocol was also demonstrated by the successful functionalization of several pharmaceuticals.
Design, synthesis and biological evaluation of O-alkyl umbelliferone derivatives as pancreatic lipase inhibitors
Yadav, Nisha,Auti, Prashant,George, Ginson,Paul, Atish T.
, p. 1265 - 1271 (2020/12/04)
A series of coumarin derivatives were synthesised through O-alkylation of umbelliferone. These derivatives were screened for their pancreatic lipase (PL) inhibitory potential. The PL inhibitory effect of compounds with various benzyl and long chain alkyl substituents on umbelliferone were analysed. The compound 1g, having the geranyl substituent was found to have better PL inhibitory potential with an IC50 of 21.64 M. The compounds 1a-j were subjected to molecular docking into the crystal structure of human PL. The molecular docking results are in correlation with the in vitro PL inhibition activity, wherein compound 1g showed a higher MolDock score of -122.12 kcal/mol. The long chain alkyl groups were found to have PL inhibition due to additional interactions with lid domain amino acids (Phe215, Tyr114, Phe77), as revealed by molecular docking study.
