3722-51-8Relevant articles and documents
The involvement of xanthone and (E)-cinnamoyl chromophores for the design and synthesis of novel sunscreening agents
Popió?, Justyna,Gunia-Krzy?ak, Agnieszka,S?oczyńska, Karolina,Koczurkiewicz-Adamczyk, Paulina,Piska, Kamil,Wójcik-Pszczo?a, Katarzyna,?elaszczyk, Dorota,Krupa, Anna,?mudzki, Pawe?,Marona, Henryk,P?kala, El?bieta
, p. 1 - 23 (2021/01/04)
Excessive UV exposure contributes to several pathological conditions like skin burns, er-ythema, premature skin aging, photodermatoses, immunosuppression, and skin carcinogenesis. Effective protection from UV radiation may be achieved with the use of sunscreens containing UV filters. Currently used UV filters are characterized by some limitations including systemic absorp-tion, endocrine disruption, skin allergy induction, and cytotoxicity. In the research centers all over the world new molecules are developed to improve the safety, photostability, solubility, and absorption profile of new derivatives. In our study, we designed and synthesized seventeen novel molecules by combining in the structures two chromophores: xanthone and (E)-cinnamoyl moiety. The ultraviolet spectroscopic properties of the tested compounds were confirmed in chloroform solutions. They acted as UVB or UVA/UVB absorbers. The most promising compound 9 (6-meth-oxy-9-oxo-9H-xanthen-2-yl)methyl (E)-3-(2,4-dimethoxyphenyl)acrylate) absorbed UV radiation in the range 290–369 nm. Its photoprotective activity and functional photostability were further evaluated after wet milling and incorporation in the cream base. This tested formulation with compound 9 possessed very beneficial UV protection parameters (SPFin vitro of 19.69 ± 0.46 and UVA PF of 12.64 ± 0.32) which were similar as broad-spectrum UV filter tris-biphenyl triazine. Additionally, compound 9 was characterized by high values of critical wavelength (381 nm) and UVA/UVB ratio (0.830) thus it was a good candidate for broad-spectrum UV filter and it might protect skin against UVA-induced photoaging. Compound 9 were also shown to be photostable, non-cytotoxic at con-centrations up to 50 μM when tested on five cell lines, and non-mutagenic in Ames test. It also possessed no estrogenic activity, according to the results of MCF-7 breast cancer model. Addition-ally, its favorable lipophilicity (miLogP = 5.62) does not predispose it to penetrate across the skin after topical application.
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors
Loh, Zi Han,Kwong, Huey Chong,Lam, Kok Wai,Teh, Soek Sin,Ee, Gwendoline Cheng Lian,Quah, Ching Kheng,Ho, Anthony Siong Hock,Mah, Siau Hui
, p. 627 - 639 (2021/02/16)
A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 μM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π–π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π–π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.
Mild C?F Activation in Perfluorinated Arenes through Photosensitized Insertion of Isonitriles at 350 nm
Weidlich, Frauke,Esumi, Naoto,Chen, Dongyang,Mück-Lichtenfeld, Christian,Zysman-Colman, Eli,Studer, Armido
supporting information, p. 376 - 383 (2019/11/19)
Fluorinated compounds have become important in the fields of agrochemical industry, pharmaceutical chemistry and materials sciences. Accordingly, various methods for their preparation have been developed in the past. Fluorinated compounds can be accessed via conjugation with fluorinated building blocks, via C?H fluorination or via selective activation of perfluorinated compounds to give the partially fluorinated congeners. Especially the direct activation of C?F bonds, one of the strongest σ-bonds, still remains challenging and new strategies for C?F activation are desirable. Herein a method for the photochemical activation of aromatic C?F bonds is presented. It is shown that isonitriles selectively insert into aromatic C?F bonds while aliphatic C?F bonds remain unaffected. Mechanistic studies reveal the reaction to proceed via the indirect excitation of the isonitrile to its triplet state by photoexcited acetophenone at 350 nm. Due to the relatively mild light used, the process shows high functional group tolerance and various compounds of the class of benzimidoyl fluorides are accessible from aryl isonitriles and commercially available perfluorinated arenes. (Figure presented.).
A Green Nanopalladium-Supported Catalyst for the Microwave-Assisted Direct Synthesis of Xanthones
Diez, Alejandra S.,Gerbino, Darío C.,Mendioroz, Pamela,Steingruber, H. Sebastián
supporting information, p. 619 - 628 (2020/02/13)
We report an efficient, selective, rapid and eco-friendly protocol for the one-step synthesis of a small xanthone library via an intermolecular catalytic coupling from readily available salicylaldehydes and 1,2-dihaloarenes under ligand-free conditions. To achieve this advantageous direct annulation, we used a novel recoverable palladium nanocatalyst supported on a green biochar under microwave irradiation. Unlike other existing palladium-based approaches, our synthetic strategy showed a greater operational simplicity, drastic reduction in reaction times, and an excellent tolerance to diverse functional groups. The reaction proceeds in very good yields and with high regioselectivity. The novel heterogeneous catalyst can be recycled and reused up to four times without significant loss of activity.
Design, synthesis and cardiovascular evaluation of some aminoisopropanoloxy derivatives of xanthone
Kubacka,Szkaradek,Mogilski,Pańczyk,Siwek,Grybo?,Filipek,?mudzki,Marona,Waszkielewicz
, p. 3773 - 3784 (2018/05/04)
A series of aminoisopropanoloxy derivatives of xanthone has been synthesized and their pharmacological properties regarding the cardiovascular system has been evaluated. Radioligand binding and functional studies in isolated organs revealed that title compounds present high affinity and antagonistic potency for α1-(compound 2 and 8), β-(compounds 1, 3, 4, 7), α1/β-(compounds 5 and 6) adrenoceptors. Furthermore, compound 7, the structural analogue of verapamil, possesses calcium entry blocking activity. The title compounds showed hypotensive and antiarrhythmic properties due to their adrenoceptor blocking effect. Moreover, they did not affect QRS and QT intervals, and they did not have proarrhythmic potential at tested doses. In addition they exerted anti-aggregation effect. The results of this study suggest that new compounds with multidirectional activity in cardiovascular system might be found in the group of xanthone derivatives.
Synthesis and molecular docking studies of xanthone attached amino acids as potential antimicrobial and anti-inflammatory agents
Chen, Xing,Leng, Jing,Rakesh,Darshini,Shubhavathi,Vivek,Mallesha,Qin, Hua-Li
, p. 1706 - 1719 (2017/08/22)
A series of novel xanthone conjugated amino acids were synthesised and characterised by analytical and spectroscopic methods. All the synthesized analogues (2-23) were screened for their in vitro antimicrobial and anti-inflammatory activities. Compounds 7, 8, 9, 12, 18, 19, 20, 21 and 23 showed excellent antimicrobial activities compared to antibacterial and antifungal reference drugs gentamicin and bavistin, respectively. Compounds 7-12 and 18-23 showed good anti-inflammatory activity compared to a standard drug, indomethacin. The preliminary structure-activity relationship revealed that tryptophan, tyrosine, phenylalanine, proline and cysteine conjugated compounds showed excellent antimicrobial and anti-inflammatory activities. This may be explained by the contribution of aromaticity and hydrophobicity of amino acids. Molecular docking studies were performed for all the synthesised compounds, among which compounds 20, 21 and 23 showed the highest docking scores for antimicrobial activity while compounds 9, 20 and 22 showed the highest docking scores for anti-inflammatory activity. Different amino acids conjugated xanthone derivatives were synthesized and evaluated for their in vitro biological activities. The conjugation was found to play a major role in improving the biological activities of those compounds.
Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties
Waszkielewicz, Anna M.,S?oczyńska, Karolina,P?kala, El?bieta,?mudzki, Pawe?,Siwek, Agata,Grybo?, Anna,Marona, Henryk
, p. 339 - 352 (2017/04/03)
A series of new xanthone derivatives have been synthesized and evaluated for their anticonvulsant properties in the maximal electroshock, subcutaneous metrazole tests and for neurotoxicity in the rotarod in mice, i.p. and rats, p.o. Compound 9: R,S-2-{2-[(1-hydroxybutan-2-yl]amino)ethoxy}-9H-xanthen-9-one and compound 12: R,S-2-{3-[(1-hydroxybutan-2-yl)amino]propoxy}-9H-xanthen-9-one exerted activity in rats, p.o. 2 and 4?h after administration, respectively. Therefore, metabolic stability of the compounds was evaluated with use of rat microsomes, resulting in half-life t1/2 136 and 108?min, respectively, indicating that either the metabolites are very active or the parent compounds exert ADME properties other than metabolism which influence the late onset of activity.
Synthesis of xanthone derivatives and studies on the inhibition against cancer cells growth and synergistic combinations of them
Liu, Jie,Zhang, Jianrun,Wang, Huailing,Liu, Zhijun,Zhang, Cao,Jiang, Zhenlei,Chen, Heru
, p. 50 - 61 (2017/04/06)
34 Xanthones were synthesized by microwave assisted technique. Their in?vitro inhibition activities against five cell lines growth were evaluated. The SAR has been thoroughly discussed. 7-Bromo-1,3-dihydroxy-9H-xanthen-9-one (3-1) was confirmed as the most active agent against MDA-MB-231?cell line growth with an IC50 of 0.46?±?0.03?μM. Combination of 3-1 and 5,6-dimethylxanthone-4-acetic acid (DMXAA) showed the best synergistic effect. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for both monomers and the combination. Western Blot implied that the combination regulated p53/MDM2 to a better healthy state. Furthermore, 3-1 and DMXAA arrested more cells on G2/M phase; while the combination arrested more cells on S phase. All the evidences support that the 3-1/DMXAA combination is a better anti-cancer therapy.
Cardiovascular activity of the chiral xanthone derivatives
Szkaradek, Natalia,Rapacz, Anna,Pytka, Karolina,Filipek, Barbara,Zelaszczyk, Dorota,Szafrański, Przemys?aw,S?oczyńska, Karolina,Marona, Henryk
, p. 6714 - 6724 (2015/10/19)
A series of 6 derivatives of xanthone were synthesized and evaluated for cardiovascular activity. The following pharmacological experiments were conducted: the binding affinity for adrenoceptors, the influence on the normal electrocardiogram, the effect on the arterial blood pressure, the effect on blood pressor response and prophylactic antiarrhythmic activity in adrenaline induced model of arrhythmia (rats, iv). Two compounds revealed nanomolar affinity for α1-adrenoceptor which was correlated with the strongest cardiovascular (antiarrhythmic and hypotensive) activity in animals' models. They were enantiomers of previously described (R,S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propoxy)-9H-xanthen-9-one hydrochloride and revealed similar antiarrhythmic potential in adrenaline induced model of arrhythmia in rats after intravenous injection (ED50 = 0.53 mg/kg and 0.81 mg/kg, respectively). These values were lower than values obtained for reference drug urapidil. These compounds were more active in this experiment than urapidil (ED50 = 1.26 mg/kg). The compound 5 administered iv at doses of 0.62-2.5 mg/kg at the peak of arrhythmia prevented and/or reduced the number of premature ventricular beats in a statistically significant manner. The ED50 value was 1.20 mg/kg. The S-enantiomer (6) given at the same doses did not show therapeutic antiarrhythmic activity in this model. These compounds significantly decreased the systolic and diastolic blood pressure throughout the whole observation period in anesthetized, normotensive rats. The studied enantiomers showed higher toxicity than urapidil, but imperceptibly higher that another cardiovascular drugs, that is, carvedilol or propranolol. They were also evaluated for mutagenic potential in the Ames (Salmonella) test. It was found that at the concentrations tested the compounds were non mutagenic when compared to solvent control. Results were quite promising and suggested that in the group of xanthone derivatives new potential antiarrhythmics and hypotensives might be found.
Microwave-assisted synthesis of xanthones promoted by ytterbium triflate
Genovese, Salvatore,Fiorito, Serena,Specchiulli, Maria Carmela,Taddeo, Vito Alessandro,Epifano, Francesco
supporting information, p. 847 - 850 (2015/01/30)
Xanthones represent a class of naturally occurring compounds with valuable and promising reported pharmacological activities. One of the main disadvantages in the use of such products is related to the difficulties in their chemical synthesis. In this Letter a new and improved method for the chemical synthesis of xanthones is described. The title compounds have been synthesized in good yields under microwave irradiation from substituted 2-hydroxybenzoic acids and phenols in the presence of Yb(OTf)3 hydrate as the catalyst.
