- The involvement of xanthone and (E)-cinnamoyl chromophores for the design and synthesis of novel sunscreening agents
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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.
- 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
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- Design, synthesis and cardiovascular evaluation of some aminoisopropanoloxy derivatives of xanthone
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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.
- Kubacka,Szkaradek,Mogilski,Pańczyk,Siwek,Grybo?,Filipek,?mudzki,Marona,Waszkielewicz
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- Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties
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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.
- Waszkielewicz, Anna M.,S?oczyńska, Karolina,P?kala, El?bieta,?mudzki, Pawe?,Siwek, Agata,Grybo?, Anna,Marona, Henryk
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p. 339 - 352
(2017/04/03)
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- Anti-Helicobacter pylori activity of some newly synthesized derivatives of xanthone
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A series of 20 xanthone derivatives was synthesized and evaluated for anti-Helicobacter pylori (H. pylori) activity. Qualitative and quantitative in vitro tests using the Kirby-Bauer method (agar disc-diffusion method) were performed. The tested compounds were screened against clarithromycin- and/or metronidazole-resistant strains of H. pylori. As a reference, Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterial strains were examined. On the basis of microbiological assays, xanthones can be considered as potential anti-H. pylori agents. They displayed significant activity against the examined strains, which was higher against the bacteria resistant to metronidazole than clarithromycin. The lowest MIC values ranging up to 20 mg l-1 were observed for the following compounds: 3, 4, 8, 9, 12, 19 (against the metronidazole-resistant strains) and the compound 10 (against the clarithromycin-resistant strain). These preliminary results for screening of xanthone derivatives form a part of an ongoing study of the structure-activity relationships of a large group of compounds. Microbiological assays will be conducted afterwards to determine the mechanism of xanthones' action against H. pylori.
- Klesiewicz, Karolina,Karczewska, Elzbieta,Budak, Alicja,Marona, Henryk,Szkaradek, Natalia
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p. 825 - 834
(2016/12/09)
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- Cardiovascular activity of the chiral xanthone derivatives
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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.
- Szkaradek, Natalia,Rapacz, Anna,Pytka, Karolina,Filipek, Barbara,Zelaszczyk, Dorota,Szafrański, Przemys?aw,S?oczyńska, Karolina,Marona, Henryk
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p. 6714 - 6724
(2015/10/19)
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- Synthesis and preliminary evaluation of pharmacological properties of some piperazine derivatives of xanthone
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A series of 9 piperazine 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 and prophylactic antiarrhythmic activity in adrenaline induced model of arrhythmia (rats, iv). Three compounds revealed nanomolar affinity for α1- adrenoceptor which was correlated with the strongest cardiovascular (antiarrhythmic and hypotensive) activity in animals' models. The most promising compound was 4-(3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (12) which revealed antiarrhythmic activity with ED50 value of 0.69 mg/kg in adrenaline induced arrhythmia (rats, iv). Other synthesized xanthone derivatives, that is, (R,S)-4-(2-hydroxy-3-(4-(2- methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (10) and (R,S)-4-(2-acetoxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy) -9H-xanthen-9-one hydrochloride (11) also acted as potential antiarrhythmics in adrenaline induced model of arrhythmia in rats after intravenous injection (ED50 = 0.88 mg/kg and 0.89 mg/kg, respectively). These values were lower than values obtained for reference drugs such as propranolol and urapidil, but not carvedilol. Results were quite promising and suggested that in the group of xanthone derivatives new potential antiarrhythmics and hypotensives might be found.
- Szkaradek, Natalia,Rapacz, Anna,Pytka, Karolina,Filipek, Barbara,Siwek, Agata,Cegla, Marek,Marona, Henryk
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p. 514 - 522
(2013/02/25)
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- Pyranoxanthones: Synthesis, growth inhibitory activity on human tumor cell lines and determination of their lipophilicity in two membrane models
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The benzopyran and dihydrobenzopyran moieties can be considered as "privileged motifs" in drug discovery being good platforms for the search of new bioactive compounds. These moieties are commonly found fused to the xanthonic scaffold belonging to the bio
- Azevedo, Carlos M.G.,Afonso, Carlos M.M.,Soares, José X.,Reis, Salette,Sousa, Diana,Lima, Raquel T.,Vasconcelos, M. Helena,Pedro, Madalena,Barbosa, Jo?o,Gales, Luís,Pinto, Madalena M.M.
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p. 798 - 816
(2013/10/22)
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- Lability of the trifluoromethyl group of trifluoromethoxybenzenes under HF/Lewis acid conditions
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The trifluoromethyl functionality of trifluoromethoxybenzenes (trifluoromethyl phenyl ethers) becomes labile under HF/Lewis acid conditions. Substrates with an unsubstituted para-position shed their -CF3 groups while performing a Friedel-Crafts reaction upon another substrate molecule's trifluoromethoxy group to generate p-rosolic acids. Substrates that had blocking groups at the para-positions reacted ortho. The electron donating substituents methoxy and phenoxy interfered with the formation of rosolic acids.
- Belter, Randolph K.
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scheme or table
p. 1302 - 1307
(2011/02/22)
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- TRICYCLIC OPIOID MODULATORS
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The invention is directed to compounds of Formula (I) useful as delta and mu opioid receptor modulators. Pharmaceutical and veterinary compositions and methods of treating mild to severe pain and various diseases using compounds of the invention are also
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Page/Page column 18-19
(2008/06/13)
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- Synthesis and photochromic behavior of novel annelated 2H-chromenes derived from hydroxy-9H-xanthen-9-ones
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The synthesis of four novel pyrano-xanthenones derived from hydroxy-9H-xanthen-9-ones is described, and their photochromic properties in solution are reported. All compounds synthesized exhibit a good colorability, making them good potential dyes. The presence of the chromone system fused in the 78-position seems to lead to more stabilized colored forms.
- Coelho, Paulo J.,Carvalho, Luis M.,Silva, Jose C.,Oliveira-Campos, Ana M.F.,Samat, Andre,Guglielmetti, Robert
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p. 117 - 123
(2007/10/03)
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- POTENTIAL ANTIDEPRESSANTS: 4-(AMINOALKOXY)THIOXANTHONES
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Four different approaches were used for preparing a series of the title compounds.Reactions of the sodium salt of 4-hydroxythioxanthone (V) with dimethylaminoalkyl chlorides gave the ethers VI and VII.Partial demethylation of VII via the carbamate IX afforded the secondary amine VIII.Reactions of the 4-bromobutoxy compound XI with amines resulted in II, XII, and XIII.Reaction of V with 1-chloro-2,3-epoxypropane and the following treatment of the resulting XIV with 2-propanamine gave the amino alcohol XV.The xanthone III was obtained via XVIII similarly like II.Theproducts, especially II and III are cyclic analogues of the antidepressant and cerebral activator "bifemelane" (I) but they do not exhibit the pharmacological profile of antidepressants.
- Cervena, Irena,Holubek, Jiri,Svatek, Emil,Protiva, Miroslav
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p. 1307 - 1316
(2007/10/02)
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- Studies in Synthesis of Xanthone Derivatives: Part III+ - A New One-step Synthesis of Xanthones
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Ethyl salicylate condenses with different phenols in refluxing diphenyl ether to give various xanthones in good yields.In the case of resorcinol, hydroquinone, catechol and 3,4-xylenol corresponding phenyl salicylate derivatives are also obtained.Condensation with hydroxycoumarins affords pyranoxanthones, which can not be prepared by the Pechmann condensation of hydroxyxanthones.The structures of the intermediates and final products are established by spectral data (IR, PMR and 13C NMR).
- Patolia, Ravji J.,Trivedi, K. N.
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p. 444 - 447
(2007/10/02)
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- Pyridazines. IV. Intramolecular Cycloaddition of 3-Chloro-6-(2-allyloxyphenoxy)pyridazines
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Intramolecular cycloaddition of 3-chloro-6-(2-allyloxyphenoxy)pyridazines yielded various hydroxyxanthenes, which were also prepared by similar cycloaddition of 3-substituted-6-(2-allylphenoxy)pyridazines containing methoxy groups on their benzene rings,
- Jojima, Teruomi,Takeshiba, Hideo,Kinoto, Takao
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p. 198 - 201
(2007/10/02)
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