Identification of Hydroxyxanthones as Na/K-ATPase Ligands

Abstract

We have screened a chemical library and identified several novel structures of Na/K-ATPase inhibitors.

Ion pumps as biological targets for decavanadate

“…That it is also being used in the treatment of breast cancer emphasises the importance of the ion pumps in the regulation of calcium homeostasis and cell survival. [10][11][12][13][14][15][16][17] It is not clear if different-sized CTS also bind to the same site or as strongly, and whether they block the translocation of intracellular sodium with the same potency. 2 Other Na + /K + -ATPase inhibitors include the anti-psychotic drug chlorpromazine, the anti-malarial agent chloroquine and the antibiotic gramicidine A (IC 50 = 8 μM) ( Table 1).…”

“…2 Other Na + /K + -ATPase inhibitors include the anti-psychotic drug chlorpromazine, the anti-malarial agent chloroquine and the antibiotic gramicidine A (IC 50 = 8 μM) ( Table 1). [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] These drugs also affect other proteins, however, and the effects on the Na + /K + -ATPase are only observed for higher concentrations. 18,19 Monomeric vanadate is a well-known Na + /K + -ATPase inhibitor which is selective towards the E2P conformation.…”

Microwave-Assisted Efficient and Green Synthesis of Hydroxyxanthone in Water

“…1). [2][3][4][5] Generally, hydroxyxanthones can be achieved through condensation of the corresponding hydroxybenzoic acids with polyphenols by the Grover, Shah, and Shah (GSS) reaction. [6] However, this method is restricted to xanthones possessing a hydroxyl group at the 1-position.…”

An efficient and convenient microwave-assisted chemical synthesis of (thio)xanthones with additional in vitro and in silico characterization

“…27,28 The same has been reported for 1,3-diacetoxyxanthone and in addition, this compound can inhibit Na/K-ATPase. 32 Likewise, its analogue, 1,6-dihydroxyxanthone, possesses antihypertensive activity 31 and can inhibit α-glucosidase. 27,28 Trihydroxyxanthones, like 1,3,5-trihydroxyxanthone, has shown anticancer 33 and antimalarial activity 30 .…”

“…34 Trihydroxyxanthones have also been shown to be monoamine oxidase 25,26 and Na/K-ATPase inhibitors. 32 Finally, 1,3,7-trihydroxyxanthone also shows anticancer activity 33 and possesses monoamine oxidase, 25,26 α-glucosidase 27,28 and fatty acid synthase inhibitory activity. 35 Synthetically, xanthones are usually obtained by chemical synthesis from benzophenones or diaryl ethers under harsh reaction conditions and/or in the presence of strong acids or toxic metals.…”