100233-15-6Relevant articles and documents
Development of Anthraquinone Derivatives as Ectonucleoside Triphosphate Diphosphohydrolase (NTPDase) Inhibitors With Selectivity for NTPDase2 and NTPDase3
Baqi, Younis,Fiene, Amelie,Müller, Christa E.,Malik, Enas M.,Pelletier, Julie,Rashed, Mahmoud,Sévigny, Jean,Sch?kel, Laura
, (2020/09/17)
Ectonucleoside triphosphate diphosphohydrolases (NTPDases) catalyze the hydrolysis of nucleoside tri- and di-phosphates to mono-phosphates. The products are subsequently hydrolyzed by ecto-5′-nucleotidase (ecto-5′-NT) to nucleosides. NTPDase inhibitors have potential as novel drugs, e.g., for the treatment of inflammation, neurodegenerative diseases, and cancer. In this context, a series of anthraquinone derivatives structurally related to the anthraquinone dye reactive blue-2 (RB-2) was synthesized and evaluated as inhibitors of human NTPDases utilizing a malachite green assay. We identified several potent and selective inhibitors of human NTPDase2 and -3. Among the most potent NTPDase2 inhibitors were 1-amino-4-(9-phenanthrylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (20, PSB-16131, IC50 of 539 nM) and 1-amino-4-(3-chloro-4-phenylsulfanyl)phenylamino-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (48, PSB-2020, IC50 of 551 nM). The most potent NTPDase3 inhibitors were 1-amino-4-[3-(4,6-dichlorotriazin-2-ylamino)-4-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (42, PSB-1011, IC50 of 390 nM) and 1-amino-4-(3-carboxy-4-hydroxyphenylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (33, PSB-2046, IC50 of 723 nM). The best NTPDase2 inhibitor 20 showed a non-competitive inhibition type, while the NTPDase3 inhibitor 42 behaved as a mixed-type inhibitor. These potent compounds were found to be selective vs. other NTPDases. They will be useful tools for studying the roles of NTPDase2 and -3 in physiology and under pathological conditions.
High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y12 receptors
Baqi, Younis,Atzler, Kerstin,K?se, Meryem,Gl?nzel, Markus,Müller, Christa E.
supporting information; experimental part, p. 3784 - 3793 (2010/04/24)
Anthraquinone derivatives related to the moderately potent, nonselective P2Y12 receptor antagonist reactive blue 2 (6) have been synthesized and optimized with respect to P2Y12 receptor affinity. A radioligand binding assay utilizing human blood platelet membranes and the P2Y12 receptor-selective antagonist radioligand [3H]2-propylthioadenosine- 5′-adenylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl) anhydride ([3H]PSB-0413) was applied for compound testing. 1-Amino-2- sulfoanthraquinone derivatives bearing a (p-phenylamino) anilino substitution in the 4-position and an additional acidic function in the meta-position of the aniline ring showed high P2Y12 receptor affinity. These new anthraquinone derivatives became accessible by a recently developed copper(0)-catalyzed Ullmann coupling reaction of 1-amino-4-bromoanthraquinone derivatives with anilines in phosphate buffer under microwave irradiation. The most potent compounds exhibited Ki values of 24.9 nM (1-amino-4-[4-phenylamino-3-sulfophenylamino]-9,10-dioxo-9,10-dihydroanthracene- 2-sulfonate, PSB-0739, 39), and 21.0 nM (1-amino-4-[4-phenylamino-3- carboxyphenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, PSB-0702, 41), respectively. 1-Amino-2-sulfo-4-anilinoanthraquinone derivatives appeared to be noncytotoxic, as shown for selected derivatives at two human cell lines (melanoma and astrocytoma). Compounds 39 and 41 represent new lead structures for the development of antithrombotic drugs.
