3875-68-1Relevant academic research and scientific papers
Novel oxazolxanthone derivatives as a new type of α-glucosidase inhibitor: synthesis, activities, inhibitory modes and synergetic effect
Ding, Sen-Miao,Lan, Tian,Ye, Gao-Jie,Huang, Jia-Jun,Hu, You,Zhu, Yi-Ran,Wang, Bo
, p. 3370 - 3378 (2018)
Xanthone derivatives have shown good α-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as α-glucosidase inhibitors. Inhibition assays indicated that compounds 4–21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5–21 (IC50 = 6.3 ± 0.4–38.5 ± 4.6 μM) were more active than 1-deoxynojirimycin (IC50 = 60.2 ± 6.2 μM), a well-known α-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver–Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4:6 led to an IC50 value of 1.9 ± 0.7 μM, better than the IC50 value of 7.1 ± 0.9 μM for compound 16 and 8.6 ± 0.9 μM for compound 20.
Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi-Target Strategy
Yang, Aihong,Yu, Qiao,Ju, Hui,Song, Lulu,Kou, Xiaodi,Shen, Rui
, (2020)
Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC50=2.403±0.002 μM for AChE and IC50=31.221±0.002 μM for BuChE), and it was also a good antioxidant (IC50=2.662±0.003 μM). Enzyme kinetic studies showed that this compound was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, its copper complex showed more significant inhibitory activity for AChE (IC50=0.934±0.002 μM) and antioxidant activity (IC50=1.064±0.003 μM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood-brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.
An efficient and convenient microwave-assisted chemical synthesis of (thio)xanthones with additional in vitro and in silico characterization
Verbanac, Donatella,Jain, Subhash C.,Jain, Nidhi,Chand, Mahesh,?ip?i? Paljetak, Hana,Matija?i?, Mario,Peri?, Mihaela,Stepani?, Vi?nja,Saso, Luciano
, p. 3180 - 3185 (2012)
Xanthones and their thio-derivatives are a class of pleiotropic compounds with various reported pharmacological and biological activities. Although these activities are mainly determined in laboratory conditions, the class itself has a great potential to be utilized as promising chemical scaffold for the synthesis of new drug candidates. One of the main obstacles in utilization of these compounds was related to the difficulties in their chemical synthesis. Most of the known methods require two steps, and are limited to specific reagents not applicable to a large number of starting materials. In this paper a new and improved method for chemical synthesis of xanthones is presented. By applying a new procedure, we have successfully obtained these compounds with the desired regioselectivity in a shorter reaction time (50 s) and with better yield (>80%). Finally, the preliminary in vitro screenings on different bacterial species and cytotoxicity assessment, as well as in silico activity evaluation were performed. The obtained results confirm potential pharmacological use of this class of molecules.
Synthesis of new xanthone analogues and their biological activity test-Cytotoxicity, topoisomerase II inhibition, and DNA cross-linking study
Woo, Sangwook,Jung, Ji,Lee, Chongsoon,Kwon, Youngjoo,Na, Younghwa
, p. 1163 - 1166 (2007)
In this report, we prepared some 3-(2′,3′-epoxypropoxy)xanthones and their epoxide ring opened halohydrin analogues, and evaluated their cytotoxicity and topoisomerase II inhibition activity using doxorubicin and etoposide as references, respectively. Another xanthone compound 9, 1,3-di(2′,3′-epoxypropoxy)xanthone, was also synthesized and its DNA cross-linking property including other two biological activities investigated. The biological test results showed compound 9 possessed excellent cytotoxic and topoisomerase II inhibitory activity than other compounds tested. It also exhibited significant DNA cross-linking activities.
Synthesis and biological evaluation of C1-O-substituted-3-(3-butylamino-2-hydroxy-propoxy)-xanthen-9-one as topoisomerase IIα catalytic inhibitors
Park, Seojeong,Hong, Eunji,Kwak, Soo Yeon,Jun, Kyu-Yeon,Lee, Eung-Seok,Kwon, Youngjoo,Na, Younghwa
, p. 211 - 225 (2016)
Topoisomerase II poison blocks the transitorily generated DNA double-strand breaks (DSBs) from religation, thereby causes severe DNA damage and gene toxicity. While topoisomerase II catalytic inhibitor does not form cleavable DNA-enzyme complex because its function attributes to inhibition of the catalytic steps of the enzyme such as before generating DNA DSBs or in the last step of the catalytic cycle after religation. It has been reported that the stabilizing effect of etoposide on transient cleavable DNA-topoisomerase IIβ complex attributes to its secondary malignancy. Therefore, topoisomerase IIα has been considered as more attractive target than topoisomerase IIβ for the development of chemotherapeutic agents. In the previous work, we reported compounds I and II as novel topoisomerase IIα catalytic inhibitors targeting for ATP binding site of human topoisomerase IIα ATP-binding domain. As a continuous work, we have designed and synthesized 43 compounds of C1-O-alkyl and arylalkyl substitiuted compounds with or without methoxy group on ring A. In the topoisomerase IIα inhibitory test, among the tested C1-O-4-chlorophenethyl substituted compounds 37 and 47 were more active than others, and compound 37 showed strongest topoisomerase IIα inhibitory activity with 94.4% and 23.0% inhibition, respectively, at 100 and 20?μM. Compounds 37 and 47 have also showed much enhanced cytotoxic activity against T47D cells; IC50(μM): 0.63?±?0.01 and 0.19?±?0.02, respectively, which are stronger than reference drugs. Band depletion assay and cleavage complex assay results showed compounds 37 and 47 were potential topoisomerase IIα catalytic inhibitor with low DNA damage.
Electronic structures and population dynamics of excited states of xanthione and its derivatives
Fedunov, Roman G.,Rogozina, Marina V.,Khokhlova, Svetlana S.,Ivanov, Anatoly I.,Tikhomirov, Sergei A.,Bondarev, Stanislav L.,Raichenok, Tamara F.,Buganov, Oleg V.,Olkhovik, Vyacheslav K.,Vasilevskii, Dmitrii A.
, p. 1 - 10 (2017)
A new compound, 1,3-dimethoxy xanthione (DXT), has been synthesized and its absorption (stationary and transient) and luminescence spectra have been measured in n-hexane and compared with xanthione (XT) spectra. The pronounced broadening of xanthione vibr
Novel xanthone-polyamine conjugates as catalytic inhibitors of human topoisomerase IIα
Minniti, Elirosa,Byl, Jo Ann W.,Riccardi, Laura,Sissi, Claudia,Rosini, Michela,De Vivo, Marco,Minarini, Anna,Osheroff, Neil
, p. 4687 - 4693 (2017)
It has been proposed that xanthone derivatives with anticancer potential act as topoisomerase II inhibitors because they interfere with the ability of the enzyme to bind its ATP cofactor. In order to further characterize xanthone mechanism and generate compounds with potential as anticancer drugs, we synthesized a series of derivatives in which position 3 was substituted with different polyamine chains. As determined by DNA relaxation and decatenation assays, the resulting compounds are potent topoisomerase IIα inhibitors. Although xanthone derivatives inhibit topoisomerase IIα-catalyzed ATP hydrolysis, mechanistic studies indicate that they do not act at the ATPase site. Rather, they appear to function by blocking the ability of DNA to stimulate ATP hydrolysis. On the basis of activity, competition, and modeling studies, we propose that xanthones interact with the DNA cleavage/ligation active site of topoisomerase IIα and inhibit the catalytic activity of the enzyme by interfering with the DNA strand passage step.
Synthesis of novel xanthone analogues and their growth inhibitory activity against human lung cancer a549 cells
Dai, Jinwei,Ding, Hongmei,Huang, Lei,Li, Tiejun,Mao, Junqin,Wang, Jing,Wu, Junqi,Yu, Shichong,Zhang, Yuefan,Zhang, Yuyang
, p. 4239 - 4246 (2019)
Purpose: Xanthones demonstrated an array of pharmacological activities via non-covalent DNA interaction and have been widely utilized in new drug research. The introduction of the polar 1,2,3-triazole ring located at the C3-position of xanthone has not been reported thus far. Methods: In the present study, a series of xanthone derivatives were designed, synthesized, and characterized through1H NMR,13C NMR, and MS. The methyl thiazolyl tetrazolium method was used to evaluate the cytotoxic activity of compounds. Furthermore, the structure– activity relationship and the potential mechanism of target compounds were investigated. Results: The IC50 showed that the inhibitory activity of 18 target compounds was higher than that of the original xanthone intermediate 4. In particular, compound 1j was the most active agent against A549 cancer cells (IC50 = 32.4 ± 2.2 μM). Moreover, apoptosis analysis indicated different contributions of early/late apoptosis to cell death for compounds 1h and 1j. The results of Western blotting analysis showed that compound 1j significantly increased the expression of caspase 3, Bax, and c-Jun N-terminal kinase, and regulated p53 to a better healthy state in cancer cells. Conclusion: We synthesized several derivatives of xanthone and evaluated their cytotoxicity. The evidence suggested that compound 1j possessed greater anticancer potential for further evaluations.
Study on synthesis and biological evaluation of 3-aryl substituted xanthone derivatives as novel and potent tyrosinase inhibitors
Yu, Lihong,Chen, Liandi,Luo, Guolin,Liu, Licai,Zhu, Wenqi,Yan, Pengke,Zhang, Peiquan,Zhang, Chao,Wu, Wenhao
, p. 1232 - 1241 (2019)
Tyrosinase plays a key role in the melanin biosynthesis since it catalyzes the transformation of tyrosine into L-dopaquinone. A large number of studies have also shown that molecules to efficiently inhibit the activity of tyrosinase would be potentially used in treating many depigmentation-related disorders. In this study, we targeted a series of structure-based 3-aryl substituted xanthone derivatives in which diverse functional groups were respectively attached on 3-aromatic ring moiety as new tyrosinase inhibitors. The results demonstrated that all obtained compounds had potent tyrosinase inhibitory activities with IC50 values at micromolar range. Especially, compound 4t was found to be the most active tyrosinase inhibitor with the IC50 value of 11.3μM, uncovering that the introduction of the proper hydroxyl group in the 3-aromatic ring was beneficial for enhancing the inhibitory potency against tyrosinase. Moreover, the inhibition mechanism and inhibition kinetics studies revealed that compound 4t presented such inhibitory effect by acting as the reversible and competitive–uncompetitive mixed-II type inhibitor. Further molecular docking simulation showed that 3-aromatic ring of compound 4t was inserted into the narrow regions of binuclear copper-binding site at the bottom of the enzyme binding pocket, while the xanthone skeleton was positioned at the surface of tyrosinase. Taken together, these data suggested that such type of molecules might be utilized for the development of new and promising candidate for the treatment of depigmentation-related disorders.
Synthesis and bioactivity of novel xanthone and thioxanthone l-rhamnopyranosides
Song, Gao-Peng,Li, Su-Mei,Si, Hong-Zong,Li, Yi-Bin,Li, Ya-Sheng,Fan, Ji-Hong,Liang, Qian-Qian,He, Hui-Bing,Ye, Han-Ming,Cui, Zi-Ning
, p. 36092 - 36103 (2015)
A series of xanthone and thioxanthone rhamnopyranosides were designed and synthesized. Their in vitro cytotoxicity and topoisomerase inhibitory activity were evaluated. The bioassay results indicated that the introduction of the 2,3-di-O-acetyl-α-l-rhamno
