BIOMAT Database Logo BIOMAT Database Logo

N-phosphonocarbonylpyrrolidine derivatives of guanine: a new class of bi-substrate inhibitors of human purine nucleoside phosphorylase. 2012

Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. Flemingovo nám. 2, 166 10 Prague 6, Czech Republic. rejman@uochb.cas.cz

A complete series of pyrrolidine nucleotides, (3R)- and (3S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acids and (3S,4R)-, (3R,4S)-, (3S,4S)-, and (3R,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N-ylcarbonylphosphonic acids, were synthesized and evaluated as potential inhibitors of purine nucleoside phosphorylase (PNP) isolated from peripheral blood mononuclear cells (PBMCs) and cell lines of myeloid and lymphoid origin. Two compounds, (S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acid (2a) and (3S,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N-ylcarbonylphosphonic acid (6a), were recognized as nanomolar competitive inhibitors of PNP isolated from cell lines with K(i) values within the ranges of 16-100 and 10-24 nM, respectively. The low (MESG)K(i) and (Pi)K(i) values of both compounds for PNP isolated from PBMCs suggest that these compounds could be bisubstrate inhibitors that occupy both the phosphate and nucleoside binding sites of the enzyme.

UI MeSH Term Description Entries
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D010757 Phosphorous Acids Inorganic derivatives of phosphorus trihydroxide (P(OH)3) and its tautomeric form dihydroxyphosphine oxide (HP Phosphonic Acids,Acids, Phosphonic,Acids, Phosphorous
D011683 Purine-Nucleoside Phosphorylase An enzyme that catalyzes the reaction between a purine nucleoside and orthophosphate to form a free purine plus ribose-5-phosphate. EC 2.4.2.1. Inosine Phosphorylase,Nicotinamide Riboside Phosphorylase,Purine Nucleoside Phosphorylases,Nucleoside Phosphorylases, Purine,Phosphorylase, Inosine,Phosphorylase, Nicotinamide Riboside,Phosphorylase, Purine-Nucleoside,Phosphorylases, Purine Nucleoside,Purine Nucleoside Phosphorylase,Riboside Phosphorylase, Nicotinamide
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D006147 Guanine
D006150 Guanine Nucleotides Guanine Nucleotide,Guanosine Phosphates,Nucleotide, Guanine,Nucleotides, Guanine,Phosphates, Guanosine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
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
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

Related Publications

Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Nucleosides. 5. Synthesis of guanine and formycin B derivatives as potential inhibitors of purine nucleoside phosphorylase.
April 1993, Journal of medicinal chemistry,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Structure-activity relationships for a class of inhibitors of purine nucleoside phosphorylase.
July 1999, Journal of medicinal chemistry,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase.
November 2010, European journal of medicinal chemistry,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
[Some inhibitors of purine nucleoside phosphorylase].
January 2011, Biomeditsinskaia khimiia,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Design of purine nucleoside phosphorylase inhibitors.
November 1986, Federation proceedings,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Adenine as substrate for purine nucleoside phosphorylase.
September 1971, Canadian journal of biochemistry,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Synthesis and biological activity of a novel class of purine nucleoside phosphorylase inhibitors.
January 2000, Nucleosides, nucleotides & nucleic acids,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
New catalytic mechanism for human purine nucleoside phosphorylase.
February 2005, Biochemical and biophysical research communications,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Nucleotide analogue inhibitors of purine nucleoside phosphorylase.
February 1990, The Journal of biological chemistry,
Dominik Rejman, and Natalya Panova, and Pavel Klener, and Bokang Maswabi, and Radek Pohl, and Ivan Rosenberg
Novel multisubstrate inhibitors of mammalian purine nucleoside phosphorylase.
November 2005, Acta crystallographica. Section D, Biological crystallography,
Copied contents to your clipboard!