31005-04-6Relevant articles and documents
Oxyprenylated Phenylpropanoids Bind to MT1 Melatonin Receptors and Inhibit Breast Cancer Cell Proliferation and Migration
Hasan, Mahmud,Genovese, Salvatore,Fiorito, Serena,Epifano, Francesco,Witt-Enderby, Paula A.
, p. 3324 - 3329 (2017)
Oxyprenylated compounds (i.e., ferulic acid and coumarin derivatives) demonstrate neuroprotection and anticancer properties as reported in previous studies. We have tested the affinity of oxyprenylated ferulic acid (1-4) and umbelliferone derivatives (5-1
Gold(I)-Catalyzed Intramolecular Hydroarylation of Phenol-Derived Propiolates and Certain Related Ethers as a Route to Selectively Functionalized Coumarins and 2 H-Chromenes
Cervi, Aymeric,Vo, Yen,Chai, Christina L. L.,Banwell, Martin G.,Lan, Ping,Willis, Anthony C.
, p. 178 - 198 (2020/12/22)
Methods are reported for the efficient assembly of a series of phenol-derived propiolates, including the parent system 56, and their Au(I)-catalyzed cyclization (intramolecular hydroarylation) to give the corresponding coumarins (e.g., 1). Simple syntheses of natural products such as ayapin (144) and scoparone (145) have been realized by such means, and the first of these subject to single-crystal X-ray analysis. A related process is described for the conversion of propargyl ethers such as 156 into the isomeric 2H-chromene precocene I (159), a naturally occurring inhibitor of juvenile hormone biosynthesis.
Design of a Functional Chromene-Type Kobayashi Precursor: Gram-Scale Total Synthesis of Natural Xanthones by Highly Regioselective Aryne Annulation
Xu, Yuan-Ze,Sha, Feng,Wu, Xin-Yan
supporting information, p. 1066 - 1071 (2020/12/18)
The 2,2-dimethyl-2H-chromene motif is widely found in many bioactive molecules, and is a privileged structure in the pharmaceutical arena. We have developed a concise and regioselective approach to chromenes and chromanes through an aryne-based synthetic
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.
Chlorophyll-catalyzed photochemical regioselective coumarin C-H arylation with diazonium salts
Moazzam, Ali,Jafarpour, Farnaz
supporting information, p. 16692 - 16696 (2020/10/27)
This communication describes the development of a mild method for the cross-coupling of the C3-position of coumarin with an array of diazonium salts mediated by chlorophyll as a biocatalyst via visible light catalysis. A natural pigment such as chlorophyll is used as a green photosensitizer and environmentally benign catalyst. This general and easy procedure provides a transition-metal-free alternative for the formation of 3-aryl coumarin derivatives at room temperature with good to excellent yields. This journal is
Natural and semisynthetic oxyprenylated aromatic compounds as stimulators or inhibitors of melanogenesis
Genovese, Salvatore,Epifano, Francesco,Medina, Philippe de,Caron, Nicolas,Rives, Arnaud,Poirot, Marc,Poirot, Sandrine Silvent,Fiorito, Serena
, p. 181 - 190 (2019/03/23)
It has been very recently shown how naturally occurring oxyprenylated coumarins are effective modulators of melanogenesis. In this short communication we wish to generalize the potentialities as skin tanning or whitening agents of a wider panel of natural and semisynthetic aromatic compounds, including coumarins, cinnamic and benzoic acids, cinnamaldehydes, benzaldehyde, and anthraquinone derivatives. A total number of 43 compounds have been tested assaying their capacity to inhibit or stimulate melanin biosynthesis in cultured murine Melan A cells. The wider number of chemicals herein under investigation allowed to depict a detailed structure-activity relationship, as the following: (a) benzoic acid derivatives are slightly pigmenting agent, for which the effect is more pronounced in compounds with longer O-side chains; (b) independently from the type of substitution, cinnamic acids are able to increase melanin biosynthesis, while benzaldehydes are able to decrease it; (c) coumarins with a 3,3-dimethylallyl or shorter skeletons as substituents in position 7 are tanning agents, while coumarins with farnesyloxy groups are whitening ones; (d) double oxyprenylation in position 6 and 7 and 3,3-dimethylallyl or geranyl skeletons have slight depigmenting capacities, while farnesyl skeletons tend to marginally increase the tanning effect; (e) the presence of electron withdrawing groups (acetyl, COOH, and -Cl) and geranyl or farnesyl oxyprenylated chains respectively in positions 3 and 7 of the coumarin nucleus lead to a whitening effect, and finally (f) oxyprenylated anthraquinones have only a weak depigmenting capacity.
Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease
Joubert, Jacques,Foka, Germaine B.,Repsold, Benjamin P.,Oliver, Douglas W.,Kapp, Erika,Malan, Sarel F.
, p. 853 - 864 (2016/10/26)
A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1–25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1–8, 10–13) showing nano-molar hMAO-B inhibition (IC50: 0.5–73?nM). Limited ChE inhibitory activity was however observed for the benzyloxy series with the exception of 2 and especially 3 showing selective BuChE inhibition. From this series 3 showed the best multifunctional activity (eqBuChE IC50?=?0.96?μM, hMAO-A IC50?=?2.13?μM, hMAO-B IC50?=?0.0021?μM). Within the N-benzylpiperidine (16–19) and p-bromo-N-benzylpiperizine (21–24) series the compounds in general showed moderate ChE and MAO-B inhibitory activity. Of these compounds 19 was the most potent multifunctional agent showing good eeAChE and eqBuChE inhibition (IC50?=?9.10?μM and 5.90?μM, respectively), and relatively potent and selective hMAO-B inhibition (IC50?=?0.30?μM, SI?= >33). Molecular modeling revealed that 19 was able to bind simultaneously to the CAS, mid-gorge and PAS sites of AChE and BuChE suggesting that it will be able to inhibit AChE induced Aβ aggregation. From this study, compounds that 3 and 19 can be considered as promising multifunctional lead compounds.
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 (2017/06/28)
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.
HDAC8 INHIBITORS FOR TREATING CANCER
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Paragraph 0271, (2015/03/13)
Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.
