- DNA binding property and antitumor evaluation of xanthone with dimethylamine side chain
-
In this work, a xanthone derivative was obtained by cationic modification of the free hydroxyl group of xanthone with dimethylamine group of high pKa value. The interactions of xanthones with DNA were investigated by spectroscopic methods, electrophoretic migration assay and polymerase chain reaction test. Results indicate that xanthones can intercalate into the DNA base pairs by the hydrophobic plane and the xanthone with dimethylamine side chain may also bind the DNA phosphate framework by the basic amine alkyl chain, thus showing a better DNA binding ability than the xanthone. Furthermore, inhibition on tumor cells (ECA109, SGC7901, GLC-82) proliferation of xanthones were evaluated by MTT method. Analysis results show that the xanthone with dimethylamine side chain exhibits more effective inhibition activity against three cancer cells than the xanthone. The effects on the inhibition of tumor cells in vitro agree with the studies of DNA binding. It means that the amine alkyl chain would play an important role in its antitumor activity and DNA binding property.
- Shen, Rui,Wang, Weihua,Yang, Gengliang
-
-
Read Online
- Design, Synthesis, Computational and Biological Evaluation of Two New Series of 1, 3- and 1,6-dihydroxy Xanthone Derivatives as Selective COX-2 Inhibitors
-
Background: Over the years, the xanthone nucleus has been serving as an interesting scaffold for the design of derivatives aiming at anti-inflammatory drug development. Objective: The objective of the current work was to design and synthesize two series of novel 3-(5'-substituted pentyloxy)-1-hydroxy xanthone & 6-(5'-substituted pentyloxy)-1-hydroxy xanthone derivatives. The designed compounds were examined in vivo for anti-inflammatory activity. The effect of the synthesized xanthone derivatives on the serum expression of IL-10 and TNF-α was evaluated to understand the underlying molecular mechanisms. Methods: The title compounds were virtually designed and screened for ADME/T properties and docked onto the COX-2 protein. The synthesis of the xanthone derivatives was achieved by the condensation of salicylic acid derivatives and a suitable phenol in the presence of a mixture of phosphorus pentoxide–methanesulfonic acid as an acylation catalyst. The compounds were evaluated for in vivo anti-inflammatory activity by carrageenan induced paw edema method and serum expression of cytokines was evaluated using ELISA assays. Results: The selected compounds exhibited docking scores ranging between -10.7 to -6.8 (Kcal/mol), respectively, as compared with standard Celecoxib (-7.9 Kcal/mol) and the nonselective COX inhibitor Indomethacin (-6.4 Kcal/mol). Among the tested compounds, 9u has shown the highest activity with 65.6% reduction in edema (69.8% for Celecoxib). Immunoassay results showed a significant drop in serum TNF-α and an elevation in serum IL-10. Conclusion: The findings highlight that some of the synthesized xanthone derivatives displayed marked anti-inflammatory activity, which can be further investigated to render efficient and novel non-ulcerogenic anti-inflammatory agents.
- Chattopadhyay, Pronobesh,Das, Aparoop,Gogoi, Urvashee,Johari, Surabhi,Pathak, Manash Pratim
-
p. 884 - 914
(2022/01/31)
-
- An efficient and convenient microwave-assisted chemical synthesis of (thio)xanthones with additional in vitro and in silico characterization
-
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.
- Verbanac, Donatella,Jain, Subhash C.,Jain, Nidhi,Chand, Mahesh,?ip?i? Paljetak, Hana,Matija?i?, Mario,Peri?, Mihaela,Stepani?, Vi?nja,Saso, Luciano
-
experimental part
p. 3180 - 3185
(2012/07/14)
-
- Synthesis, SAR and biological evaluation of natural and non-natural hydroxylated and prenylated xanthones as antitumor agents
-
In order to explore the detailed structure-activity relationship (SAR) around xanthone scaffold bearing hydroxyl and prenyl moieties, twenty-nine natural and non-natural hydroxylated and prenylated xanthones have been synthesized and evaluated for their in vitro anti-proliferative activities against five human cancer cell lines, including HepG2 (hepatocelluar carcinoma), HCT-116 (colon carcinoma), A549 (lung carcinoma), BGC823 (gastric carcinoma) and MDAMB- 231 (breast carcinoma). The SAR analysis revealed that the anti-proliferative activity of the xanthones is substantially influenced by the position and number of attached hydroxyl and prenyl groups, and the presence of hydroxyl group ortho to the carbonyl function of xanthone scaffold contributes significantly to their cytotoxicity. The new prenylated xanthone 20 with a relatively simple structure, namely 1,3,8-trihydroxy-2-prenylxanthone, was found to exhibit potent antitumor activities comparable to mangostin against all the five cancer cell lines. Further mechanistic studies suggested that compound 20 induces apoptosis and causes cell cycle arrest at S phase in HepG2 cells. These results have highlighted compound 20 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents.
- Zhang, Xiaojin,Li, Xiang,Tao, Lei,Gao, Yuan,Gong, Dandan,Xi, Meiyang,Xu, Xiaoli,Guo, Qinglong,You, Qidong,Ye, Suofu,Zhang, Yu,Meng, Huyan,Zhang, Mingqian,Gao, Wenlei
-
p. 1012 - 1025,14
(2012/12/12)
-
- Excited-state intramolecular proton transfer in 2-(2′,6′-dihydroxyphenyl)benzoxazole: effect of dual hydrogen bonding on the optical properties
-
2-(2′,6′-Dihydroxyphenyl)benzoxazole (DHBO) has been synthesized by using palladium-catalyzed oxidative cyclization. The compound utilizes both O-H···N and O-H···O bonds to ensure a coplanar structure between the benzoxazole and phenol fragments. Optical comparison with the parent compound 2-(2′-hydroxyphenyl)benzoxazole (HBO) reveals that the dual hydrogen bonding in DHBO plays an essential role in raising the desirable keto emission for ESIPT and tuning the polarity sensitivity toward the molecular environment. DHBO also exhibits a higher quantum yield (φ{symbol}fl = 0.108 in methanol) than HBO (φ{symbol}fl = 0.0025) in the same solvent.
- Chen, Wei-Hua,Pang, Yi
-
experimental part
p. 1914 - 1918
(2010/09/07)
-
- Synthesis and pharmacological activities of xanthone derivatives as α-glucosidase inhibitors
-
Considerable interest has been attracted in xanthone and its derivatives because of their large variety of pharmacological activities. In this project, a series of hydroxylxanthones and their acetoxy and alkoxy derivatives were synthesized and evaluated a
- Liu, Yan,Zou, Lan,Ma, Lin,Chen, Wen-Hua,Wang, Bo,Xu, Zun-Le
-
p. 5683 - 5690
(2007/10/03)
-
- γ-Pyrone compounds. IV: Synthesis and antiplatelet effects of mono- and dioxygenated xanthones and xanthonoxypropanolamine
-
Xanthodilol, mono- and dioxygenated xanthones, and 1,3-, 2,3-, 3,4-, 3,5- , 1,6-, 2,6-, and 3,6-dioxygenated xanthones were synthesized from benzophenone precursors by Friedel-Crafts acylation and subsequent base- catalyzed cyclization to eliminate methanol. 3-Hydroxyxanthone, xanthodilol, 2,3-dihydroxyxanthone diacetate, and 3,4-dihydroxyxanthone and its diacetate showed potent antiplatelet effects on arachidonate- and collagen-induced aggregation. 3,5-Dihydroxyxanthone and its diacetate, 1,6-dimethoxyxanthone, and 3,6-dihydroxyxanthone and its diacetate showed potent antiplatelet effects on arachidonate-induced aggregation.
- Lin,Liou,Ko,Teng
-
-
- Agent for inhibiting binding of 5-dihydro-testosterone with androgen receptor as well as process for obtaining same
-
An agent for inhibiting the binding of 5α-dihydrotestosterone with androgen receptor, which comprises at least one extract from herbs or one of specific xanthone compounds, and a process for obtaining the agent.
- -
-
-
- Studies in synthesis of xanthones: Part VIII
-
Thermal condensation of the methyl esters of 2,6-dihydroxy-, 2,4-dihydroxy- and 2,4,6-trihydroxy-benzoic acids has been carried out with different phenols in refluxing diphenyl ether to give various xanthones in good yields.Condensation of methyl 5-bromo-2-hydroxybenzoate with hydroquinone gives 7-bromo-1,4-dihydroxyxanthone (19) and 7-bromo-2-hydroxyxanthone (20).However, condensation of methyl 5-chloro-2,6-dihydroxybenzoate with phloroglucinol gives 5-chloro-1,3,8-trihydroxyxanthone (21).The structures of these products have been established by IR, mass and PMR spectral studies.
- Patel G N,Trivedi K N
-
p. 437 - 439
(2007/10/02)
-
- A CONVENIENT SYNTHESIS OF NATURALLY OCCURING XANTHONES
-
Six naturally occuring xanthones are synthesized by the thermal condensation of methyl 2,6-dihydroxybenzoate, methyl 2,4-dihydroxybenzoate and methyl 2,4,6-trihydroxybenzoate with hydroquinone, catechol and pyrogallol.
- Patel, G. N.,Trivedi, K. N.
-
p. 1641 - 1648
(2007/10/02)
-