BIOMAT Database Logo BIOMAT Database Logo

Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. 2010

Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, Pharmaceutical Sciences Bonn, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.

ecto-5'-Nucleotidase (eN, CD73) plays a major role in controlling extracellular adenosine levels. eN inhibitors have potential as novel drugs, for example, for the treatment of cancer. In the present study, we synthesized and investigated a series of 55 anthraquinone derivatives as potential inhibitors of eN, 11 of which are novel compounds and another 11 of which had previously been described but have now been synthesized by an improved method. We identified several potent inhibitors of rat eN. The most potent compounds were 1-amino-4-[4-fluoro-2-carboxyphenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (45, PSB-0952, K(i) = 260 nM) and 1-amino-4-[2-anthracenylamino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate (52, PSB-0963, 150 nM), with 52 being the most potent eN inhibitor described to date. Selected compounds were further characterized and found to exhibit a competitive mechanism of inhibition. Investigations of ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) and the P2Y receptor subtypes P2Y(2), P2Y(4), P2Y(6), and P2Y(12) showed that compound 45 exhibited the highest degree of selectivity (>150-fold).

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D011983 Receptors, Purinergic Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP. Methyladenine Receptors,Purine Receptors,Purinergic Receptor,Purinergic Receptors,Purinoceptors,Purine Receptor,Purinoceptor,Receptors, Methyladenine,Receptors, Purine,Receptor, Purine,Receptor, Purinergic
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000814 Aniline Compounds Compounds that include the aminobenzene structure. Phenylamine,Phenylamines,Anilines,Compounds, Aniline
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000880 Anthraquinones Compounds based on ANTHRACENES which contain two KETONES in any position. Substitutions can be in any position except on the ketone groups. Anthracenedione,Anthracenediones,Anthranoid,Anthraquinone,Anthraquinone Compound,Anthraquinone Derivative,Dianthraquinones,Dianthrones,Anthranoids,Anthraquinone Compounds,Anthraquinone Derivatives,Compound, Anthraquinone,Derivative, Anthraquinone
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015720 5'-Nucleotidase A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5. 5'-AMP Nucleotidase,AMP Phosphatase,Adenylate Phosphatase,Antigens, CD73,CD73 Antigens,Cytidylate Phosphatase,Ecto-5'-Nucleotidase,IMP Nucleotidase,IMP Phosphatase,Inosinate Phosphatase,Pyrimidine 5'-Nucleotidase,Thymidine Phosphatase,Uridylate 5'-Nucleotidase,5'-Nucleotidase Phosphoribolase,Antigen, CD73,IMPase,5' AMP Nucleotidase,5' Nucleotidase,5' Nucleotidase Phosphoribolase,CD73 Antigen,Ecto 5' Nucleotidase,Pyrimidine 5' Nucleotidase,Uridylate 5' Nucleotidase
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

Related Publications

Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Polyoxometalates--potent and selective ecto-nucleotidase inhibitors.
January 2015, Biochemical pharmacology,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5'-Nucleotidase (CD73) Inhibitors.
August 2015, Journal of medicinal chemistry,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Isonicotinohydrazones as inhibitors of alkaline phosphatase and ecto-5'-nucleotidase.
March 2017, Chemical biology & drug design,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Identification of sulfonic acids as efficient ecto-5'-nucleotidase inhibitors.
January 2013, European journal of medicinal chemistry,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Virtual screening identifies novel sulfonamide inhibitors of ecto-5'-nucleotidase.
July 2012, Journal of medicinal chemistry,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Therapeutic potentials of ecto-nucleoside triphosphate diphosphohydrolase, ecto-nucleotide pyrophosphatase/phosphodiesterase, ecto-5'-nucleotidase, and alkaline phosphatase inhibitors.
July 2014, Medicinal research reviews,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
[Purine ecto-5'-nucleotidase deficiency].
January 1998, Ryoikibetsu shokogun shirizu,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Development of a fast CE method for high throughput screening of ecto-5'-nucleotidase inhibitors.
October 2018, Electrophoresis,
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Identification of small molecule sulfonic acids as ecto-5'-Nucleotidase inhibitors.
November 2012, Medicinal chemistry (Shariqah (United Arab Emirates)),
Younis Baqi, and Sang-Yong Lee, and Jamshed Iqbal, and Peter Ripphausen, and Anne Lehr, and Anja B Scheiff, and Herbert Zimmermann, and Jürgen Bajorath, and Christa E Müller
Discovery of highly selective and potent p38 inhibitors based on a phthalazine scaffold.
October 2008, Journal of medicinal chemistry,
Copied contents to your clipboard!