Antonin Holy

Summary

Affiliation: Institute of Organic Chemistry and Biochemistry
Country: Czech Republic

Publications

  1. ncbi request reprint Structure-antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues. 1. Derivatives substituted at the carbon atoms of the base
    A Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, 16610 Praha 6, Czech Republic
    J Med Chem 42:2064-86. 1999
  2. ncbi request reprint [Antiviral agents in 2000--and then what next?]
    A Holy
    Ustav organické chemie a biochemie AV CR, Praha
    Cas Lek Cesk 140:583-91. 2001
  3. ncbi request reprint O-Phosphonatomethylcholine, its analogues, alkyl esters, and their biological activity
    A Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ 16610 Praha 6, Czech Republic
    J Med Chem 44:4462-7. 2001
  4. ncbi request reprint Antiviral acyclic nucleoside phosphonates structure activity studies
    Antonin Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Centre for Novel Antivirals and Antineoplastics, 166 10 Praha 6, Czech Republic
    Antiviral Res 71:248-53. 2006
  5. ncbi request reprint 6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity
    Antonin Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, CZ 166 10 Praha 6, Czech Republic
    J Med Chem 45:1918-29. 2002
  6. ncbi request reprint Phosphonomethoxyalkyl analogs of nucleotides
    Antonin Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ 16610 Praha 6, Flemingovo nam 2
    Curr Pharm Des 9:2567-92. 2003
  7. ncbi request reprint 5-Substituted-2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidines-acyclic nucleoside phosphonate analogues with antiviral activity
    Dana Hocková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, CZ 166 10, Prague 6, Czech Republic
    J Med Chem 46:5064-73. 2003
  8. ncbi request reprint Ester prodrugs of cyclic 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity
    Marcela Krečmerová
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
    J Med Chem 50:5765-72. 2007
  9. ncbi request reprint Synthesis of guanidino analogues of PMPDAP and their immunobiological activity
    Michal Cesnek
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i, Flemingovo nam 2, 166 10 Praha 6, Czech Republic
    Bioorg Med Chem 16:965-80. 2008
  10. ncbi request reprint Nucleotide analogues with immunobiological properties: 9-[2-Hydroxy-3-(phosphonomethoxy)propyl]-adenine (HPMPA), -2,6-diaminopurine (HPMPDAP), and their N6-substituted derivatives
    Petr Potmesil
    Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Centre for New Antivirals and Antineoplastics, Videnska 1083, 142 20 Prague 4, Czech Republic
    Eur J Pharmacol 540:191-9. 2006

Collaborators

Detail Information

Publications56

  1. ncbi request reprint Structure-antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues. 1. Derivatives substituted at the carbon atoms of the base
    A Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, 16610 Praha 6, Czech Republic
    J Med Chem 42:2064-86. 1999
    ..Also, the diisopropyl and diisooctyl ester of PMEDAP inhibited CMV and VZV, but esterification of the phosphonate residue did not improve the activity against either MSV or HIV...
  2. ncbi request reprint [Antiviral agents in 2000--and then what next?]
    A Holy
    Ustav organické chemie a biochemie AV CR, Praha
    Cas Lek Cesk 140:583-91. 2001
    ..Drugs in clinical development are aimed at enteroviruses and hepatitis C, as well as at resistant mutants of HIV, HBV and VZV...
  3. ncbi request reprint O-Phosphonatomethylcholine, its analogues, alkyl esters, and their biological activity
    A Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ 16610 Praha 6, Czech Republic
    J Med Chem 44:4462-7. 2001
    ..In vivo evaluation of hexadecyl O-phosphonomethylcholine [transplanted SD lymphoma in inbred SD/cub rats, 10 mg kg(-1) day(-1) intratumoral injection for 10 days] resulted in a 40% decrease in lymphoma mass...
  4. ncbi request reprint Antiviral acyclic nucleoside phosphonates structure activity studies
    Antonin Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Centre for Novel Antivirals and Antineoplastics, 166 10 Praha 6, Czech Republic
    Antiviral Res 71:248-53. 2006
    ..In addition to these "classical compounds" the review describes the present development in the field of ANP, the "open-ring ANP" and discusses the present achievements, concept of prodrug design and application...
  5. ncbi request reprint 6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity
    Antonin Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, CZ 166 10 Praha 6, Czech Republic
    J Med Chem 45:1918-29. 2002
    ..In analogy to N(9)-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), solely the (R)-2,4-diamino-6-[2-(phosphonomethoxy)propoxy]pyrimidine exerted antiviral activity, whereas its (S)-enantiomer was essentially inactive...
  6. ncbi request reprint Phosphonomethoxyalkyl analogs of nucleotides
    Antonin Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ 16610 Praha 6, Flemingovo nam 2
    Curr Pharm Des 9:2567-92. 2003
    ..Three compounds of the ANP group (cidofovir, adefovir, tenofovir) are active components of potent antivirals approved for therapeutic use in human medicine aimed at hepatitis B, AIDS and various diseases caused by DNA viruses...
  7. ncbi request reprint 5-Substituted-2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidines-acyclic nucleoside phosphonate analogues with antiviral activity
    Dana Hocková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, CZ 166 10, Prague 6, Czech Republic
    J Med Chem 46:5064-73. 2003
    ..0023-0.0110 mumol/mL), comparable to that of the reference drugs adefovir and tenofovir, but were devoid of measurable toxicity at 0.3 mumol/mL...
  8. ncbi request reprint Ester prodrugs of cyclic 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity
    Marcela Krečmerová
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
    J Med Chem 50:5765-72. 2007
    ..The relative configuration of the diastereoisomer trans-6 was determined using H,H-NOESY NMR...
  9. ncbi request reprint Synthesis of guanidino analogues of PMPDAP and their immunobiological activity
    Michal Cesnek
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i, Flemingovo nam 2, 166 10 Praha 6, Czech Republic
    Bioorg Med Chem 16:965-80. 2008
    ..The most active compounds are 27 and 54. None of the compounds tested exhibited any significant cytostatic effect or antiviral effect...
  10. ncbi request reprint Nucleotide analogues with immunobiological properties: 9-[2-Hydroxy-3-(phosphonomethoxy)propyl]-adenine (HPMPA), -2,6-diaminopurine (HPMPDAP), and their N6-substituted derivatives
    Petr Potmesil
    Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Centre for New Antivirals and Antineoplastics, Videnska 1083, 142 20 Prague 4, Czech Republic
    Eur J Pharmacol 540:191-9. 2006
    ..The immunomodulatory effects were found to be at least in part dependent on P1 purinoreceptors, and mediated by transcriptional factor nuclear factor-kappaB...
  11. doi request reprint The effect of novel [3-fluoro-(2-phosphonoethoxy)propyl]purines on the inhibition of Plasmodium falciparum, Plasmodium vivax and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferases
    Ondřej Baszczyňski
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i, Flemingovo nam 2, CZ 166 10 Prague 6, Czech Republic
    Eur J Med Chem 67:81-9. 2013
    ..Possible explanations for these changes in affinity are proposed based on docking studies using the known crystal structures of human HGPRT in complex with PEEG. ..
  12. pmc Acyclic nucleoside bisphosphonates: synthesis and properties of chiral 2-amino-4,6-bis[(phosphonomethoxy)alkoxy]pyrimidines
    Petra Doláková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i Flemingovo nám 2, CZ 166 10 Prague 6, Czech Republic
    Eur J Med Chem 44:2408-24. 2009
    ..The enantiomeric purity of selected compounds was determined by capillary electrophoresis. Antiviral activity of bisphosphonates is discussed...
  13. ncbi request reprint Antiviral activity of triazine analogues of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (cidofovir) and related compounds
    Marcela Krečmerová
    Gilead Sciences and IOCB Research Centre, Centre for New Antivirals and Antineoplastics IOCB, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
    J Med Chem 50:1069-77. 2007
    ..Decomposition of 1 in alkaline solutions resulted in products 17 and 18. While the N-formylguanidine derivative 17 proved active, the carbamyolguanidine derivative 18 was devoid of antiviral activity...
  14. doi request reprint Acyclic nucleoside phosphonates with a branched 2-(2-phosphonoethoxy)ethyl chain: efficient synthesis and antiviral activity
    Dana Hocková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ 16610 Prague 6, Czech Republic
    Bioorg Med Chem 19:4445-53. 2011
    ..Adenine as a nucleobase and the methyl group attached to the PEE chain proved to be a prerequisite to afford pronounced antiviral activity...
  15. doi request reprint Synthesis of 9-phosphonoalkyl and 9-phosphonoalkoxyalkyl purines: evaluation of their ability to act as inhibitors of Plasmodium falciparum, Plasmodium vivax and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferases
    Michal Cesnek
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic, Flemingovo nam 2, 166 10 Prague 6, Czech Republic
    Bioorg Med Chem 20:1076-89. 2012
    ..The chemical nature of the purine base also effects the K(i) values. This data shows that both the linker and the purine base play an important role in the binding of the ANPs to these three enzymes...
  16. ncbi request reprint Tricyclic etheno analogs of PMEG and PMEDAP: synthesis and biological activity
    Katerina Horejsí
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, CZ 166 10 Praha 6, Czech Republic
    Bioorg Med Chem 14:8057-65. 2006
    ..None of the compounds tested exhibited any significant cytostatic effect...
  17. doi request reprint Synthesis of purine N9-[2-hydroxy-3-O-(phosphonomethoxy)propyl] derivatives and their side-chain modified analogs as potential antimalarial agents
    Marcela Krečmerová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i, Flemingovo nam 2, CZ 166 10 Prague 6, Czech Republic
    Bioorg Med Chem 20:1222-30. 2012
    ..This suggests that the covalent attachment of a second group to the ANPs mimicking pyrophosphate and occupying its binding pocket could increase the affinity for these enzymes...
  18. doi request reprint New prodrugs of Adefovir and Cidofovir
    Tomas Tichy
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 166 10, Czech Republic
    Bioorg Med Chem 19:3527-39. 2011
    ..S)-HPMPC prodrugs exhibited anti-cytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir...
  19. ncbi request reprint Cytostatic activity of antiviral acyclic nucleoside phosphonates in rodent lymphocytes
    Zdenek Zidek
    Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic
    Toxicol Appl Pharmacol 192:246-53. 2003
    ..036 microM). The N(6)-substituted derivatives of (S)-PMPA are virtually devoid of cytostatic activity. No tight correlation between the cytostatic and reported antiviral effects could be detected...
  20. ncbi request reprint Synthesis of base substituted 2-hydroxy-3-(purin-9-yl)-propanoic acids and 4-(purin-9-yl)-3-butenoic acids
    Petra Doláková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Praha, Czech Republic
    Nucleosides Nucleotides Nucleic Acids 22:2145-60. 2003
    ..Reaction of compounds 3 with malonic acid in aqueous solution gave exclusively the product of isomerisation, 6-substituted 4-(purin-9-yl)-3-butenoic acids (15)...
  21. doi request reprint Synthesis and antiviral activity of N9-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N6-substituted adenines and 2,6-diaminopurines
    Ondřej Baszczyňski
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i Flemingovo nám 2, 16610 Prague 6, Czech Republic
    Bioorg Med Chem 19:2114-24. 2011
    ....
  22. doi request reprint Syntheses of N3-substituted thymine acyclic nucleoside phosphonates and a comparison of their inhibitory effect towards thymidine phosphorylase
    Karel Pomeisl
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i, Centre for New Antivirals and Antineoplastics IOCB, Prague, Czech Republic
    Bioorg Med Chem Lett 18:1364-7. 2008
    ..None of the presented N(3)-substituted derivatives possess a significant cytostatic activity...
  23. doi request reprint A novel and efficient one-pot synthesis of symmetrical diamide (bis-amidate) prodrugs of acyclic nucleoside phosphonates and evaluation of their biological activities
    Petr Jansa
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic vvi, Flemingovo nam 2, 16610 Prague 6, Czech Republic
    Eur J Med Chem 46:3748-54. 2011
    ..Anti-HIV, antiproliferative, and immunomodulatory activities of the compounds are discussed including the bis-amidate prodrugs 14 and 17 that exhibited anti-HIV activity at submicromolar concentrations with minimal cytotoxicity...
  24. ncbi request reprint Discovery of 5-substituted-6-chlorouracils as efficient inhibitors of human thymidine phosphorylase
    Radim Nencka
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Centre for New Antivirals and Antineoplastics, Flemingovo nam 2, Prague 6, Czech Republic
    J Med Chem 50:6016-23. 2007
    ..20 +/- 0.03 microM (Ki/dThdKm = 0.0017) for thymidine phosphorylase expressed in V79 cells and Ki = 0.29 +/- 0.04 microM (Ki/dThdKm = 0.0024) for the enzyme purified from placenta...
  25. doi request reprint Chiral analysis of anti-acquired immunodeficiency syndrome drug, 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir), and related antiviral acyclic nucleoside phosphonates by CE using beta-CD as chiral selector
    Veronika Solínová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Electrophoresis 30:2245-54. 2009
    ..Using the UV-absorption detection at 206 nm, the concentration detection limits of the analyzed acyclic nucleoside phosphonates were determined in the submicromolar to micromolar range (0.15-2.51 microg/mL level)...
  26. doi request reprint Design, synthesis, and biological evaluation of novel coxsackievirus B3 inhibitors
    Michal Sála
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Bioorg Med Chem 18:4374-84. 2010
    ..The synthesis and biological evaluation of 31 target compounds are described. Several of the analogues inhibited CVB3 in the low micromolar range (0.66-2muM). Minimal or no cytotoxicity was observed...
  27. ncbi request reprint Distinct modulation of telomere length in two T-lymphoblastic leukemia cell lines by cytotoxic nucleoside phosphonates PMEG and PMEDAP
    Miroslav Hájek
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
    Eur J Pharmacol 643:6-12. 2010
    ..It is neither due to direct telomerase inhibition nor impairment of hTERT expression and it is likely to be telomerase-independent...
  28. ncbi request reprint Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds
    Dana Hocková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, CZ 166 10 Prague 6, Czech Republic
    Bioorg Med Chem 12:3197-202. 2004
    ..The 5-cyano and 5-formyl derivatives showed pronounced antiretroviral activity, comparable to that of the reference drugs adefovir and tenofovir...
  29. ncbi request reprint Syntheses of pyrimidine acyclic nucleoside phosphonates as potent inhibitors of thymidine phosphorylase (PD-ECGF) from SD-lymphoma
    Karel Pomeisl
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Nucleosides Nucleotides Nucleic Acids 26:1025-8. 2007
    ..The obtained compounds exhibit a considerable inhibitory potency of thymidine phosphorylase from SD-lymphoma. In contrast, the synthesized phosphonates are not efficient inhibitors of E. coli and human thymidine phosphorylase...
  30. ncbi request reprint Synthesis of 9-alkyl and 9-heteroalkyl substituted 2-amino-6-guanidinopurines and their influence on the NO-production in macrophages
    Michal Cesnek
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, 166 10 Praha 6, Czech Republic
    Bioorg Med Chem 13:2917-26. 2005
    ..The activity of the thus prepared compounds on murine macrophages was examined. Compounds 4a, 4b, and 4d inhibit the LPS+IFN-gamma-induced NO production in murine macrophages while compound 4h stimulates this production...
  31. ncbi request reprint Design and synthesis of novel 5,6-disubstituted uracil derivatives as potent inhibitors of thymidine phosphorylase
    Radim Nencka
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
    Bioorg Med Chem Lett 16:1335-7. 2006
    ..Bis-uracil conjugates were identified as the most potent inhibitors of TPs in this study...
  32. ncbi request reprint Secretion of antiretroviral chemokines by human cells cultured with acyclic nucleoside phosphonates
    Zdenek Zidek
    Institute of Experimental Medicine, Department of Pharmacology, Academy of Sciences of the Czech Republic, Prague 4, Czech Republic
    Eur J Pharmacol 574:77-84. 2007
    ..It may be suggested that acyclic nucleoside phosphonates represent a new generation of antivirotics with combined antimetabolic and therapeutically prospective immunostimulatory properties...
  33. ncbi request reprint Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3
    Petr Potmesil
    Institute of Experimental Medicine, Department of Immunopharmacology, Academy of Sciences of the Czech Republic, Centre for New Antivirals and Antineoplastics, Prague 4, Czech Republic
    J Biomed Sci 14:59-66. 2007
    ..Enhancement of monocyte chemotactic protein expression was found to be mediated by transcriptional factor nuclear factor-kappaB (NF-kappaB)...
  34. doi request reprint An enzymatic glycosylation of nucleoside analogues using β-galactosidase from Escherichia coli
    Jiří Blažek
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic, v v i, Flemingovo namesti 2, CZ 166 10 Prague 6, Czech Republic
    Bioorg Med Chem 20:3111-8. 2012
    ....
  35. ncbi request reprint Involvement of MAP kinases in the cytotoxicity of acyclic nucleoside phosphonates
    Helena Mertlíková-Kaiserová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, 166 10 Prague 6, Czech Republic
    Anticancer Res 32:497-501. 2012
    ..9-[2-(phosphonomethoxy)ethyl] guanine (PMEG) is a nucleotide analogue with anticancer activity. Here we investigate the role of ERK, p38, JNK and AKT kinases in PMEG-induced apoptosis...
  36. ncbi request reprint Synthesis and immunobiological activity of base substituted 2-amino-3-(purin-9-yl)propanoic acid derivatives
    Petra Doláková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Bioorg Med Chem 13:2349-54. 2005
    ..Most of these compounds also augmented NO biosynthesis triggered primarily by IFN-gamma...
  37. doi request reprint Study of chemical stability of antivirally active 5-azacytosine acyclic nucleoside phosphonates using NMR spectroscopy
    Martin Dracinsky
    Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v v i, Flemingovo nam 2, CZ 166 10 Prague 6, Czech Republic
    Bioorg Med Chem 16:6778-82. 2008
    ..The reaction pathway of HPMP-5-azaC involves a formyl derivative formed by intramolecular transformylation reaction...
  38. doi request reprint Acyclic nucleoside phosphonates with 5-azacytosine base moiety substituted in C-6 position
    Marcela Krečmerová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, vvi, Gilead Sciences and IOCB Research Centre, Flemingovo nam 2, CZ 166 10, Prague 6, Czech Republic
    Bioorg Med Chem 18:387-95. 2010
    ..Surprisingly, N-3 isomer of 6-methyl-HPMP-5-azaC in the form of isopropyl ester revealed activity against RNA viruses (Sindbis virus)...
  39. ncbi request reprint Determination of acid-base dissociation constants of amino- and guanidinopurine nucleotide analogs and related compounds by capillary zone electrophoresis
    Veronika Solínová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Electrophoresis 27:1006-19. 2006
    ..75-10.32, pKa of phosphonic acid to the second dissociation degree achieved values of 6.64-7.46, and pKa of protonated nitrogen in position 1 of purine was in the range of 4.13-4.89, depending on the structure of the analyzed compounds...
  40. doi request reprint Determination of the antioxidative activity of substituted 5-aminopyrimidines
    Eliška Procházková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, Prague, Czech Republic
    Free Radic Res 46:61-7. 2012
    ..In summary, we have identified the antioxidant activity of a series of substituted 5-aminopyrimidines and their potential prodrugs which may have implications in the treatment of oxidative stress-related diseases...
  41. ncbi request reprint The substrate activity of (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine diphosphate toward DNA polymerases alpha, delta and epsilon
    Gabriel Birkus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Antivir Chem Chemother 15:23-33. 2004
    ..These observations indicate that interaction of HPMPApp with pol alpha, delta and epsilon may contribute to its cellular toxicity and explain its antiviral activity against polyomavirus...
  42. doi request reprint Point mutations in human guanylate kinase account for acquired resistance to anticancer nucleotide analogue PMEG
    Helena Mertlíková-Kaiserová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague
    Biochem Pharmacol 82:131-8. 2011
    ..Therefore, PMEG is unlikely to cause cross-resistance in combination therapeutic protocols with most other commonly used anticancer drugs...
  43. ncbi request reprint Role of caspases and CD95/Fas in the apoptotic effects of a nucleotide analog PMEG in CCRF-CEM cells
    Helena Mertlíková-Kaiserová
    Institute of Organic Chemistry and Biochemistry AS CR, Flemingovo nam 2, 166 10 Prague 6, Czech Republic
    Anticancer Res 30:2791-8. 2010
    ..The objective of this study was to determine the requirements for caspase and CD95/Fas activation in PMEG-induced apoptosis. Additionally, the influence of PMEG on cell cycle regulatory proteins was explored...
  44. doi request reprint Synthesis of branched 9-[2-(2-phosphonoethoxy)ethyl]purines as a new class of acyclic nucleoside phosphonates which inhibit Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
    Dana Hocková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, Prague 6 166 10, Czech Republic
    Bioorg Med Chem 17:6218-32. 2009
    ..The best inhibitor of PfHGXPRT has a K(i) of 1 microM. The data showed that both the position and nature of the hydrophobic substituent change the potency and selectivity of the ANPs...
  45. ncbi request reprint Inhibition of thymidine phosphorylase (PD-ECGF) from SD-lymphoma by phosphonomethoxyalkyl thymines
    Ivan Votruba
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague, Czech Republic
    Biochem Pharmacol 69:1517-21. 2005
    ..0026 for (R)-FPMPT and 0.0048 for (S)-FPMPT. The studied compounds do not inhibit Escherichia coli and human enzyme and possess lower inhibitory potency against rat liver thymidine phosphorylase...
  46. ncbi request reprint Synthesis and antiproliferative activity of 2,6-diamino-9-benzyl-9-deazapurine and related compounds
    Miroslav Otmar
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, 166 10 Prague 6, Czech Republic
    Bioorg Med Chem 12:3187-95. 2004
    ..The most potent compounds were the above mentioned 6-dibromomethyl derivative (IC(50)=0.54, 1.7, 5.0, and 1.9 molL(-1)) and 7,N(2),N(4)-tribenzyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine (IC(50)=1.9, 2.7, 7.3, and 1.0 molL(-1))...
  47. doi request reprint Compound instability in dimethyl sulphoxide, case studies with 5-aminopyrimidines and the implications for compound storage and screening
    Eliška Procházková
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Bioorg Med Chem Lett 22:6405-9. 2012
    ..DMSO is often used as the solvent in in vitro tests of biological activities, but it is also an oxidising agent and may react with solute molecules and significantly affect the quality of the generated biochemical data...
  48. doi request reprint Antiviral activity of tenofovir against Cauliflower mosaic virus and its metabolism in Brassica pekinensis plants
    Josef Spak
    Biology Centre, v v i, Institute of Plant Molecular Biology, Academy of Sciences of the Czech Republic, Branisovska 31, 37005 Ceske Budejovice, Czech Republic
    Antiviral Res 92:378-81. 2011
    ..The extent of phosphorylation in the plant's leaves represents only 4.5% of applied labeled (R)-PMPA. In roots, we detected no radioactive peaks of phosphorylated metabolites of (R)-PMPAp or (R)-PMPApp...
  49. ncbi request reprint Inhibition of human telomerase by diphosphates of acyclic nucleoside phosphonates
    Miroslav Hájek
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
    Biochem Pharmacol 70:894-900. 2005
    ..The data may contribute to the rational design of telomerase inhibitors based on the structure of acyclic nucleotide analogues...
  50. ncbi request reprint N6-methyl-AMP aminohydrolase activates N6-substituted purine acyclic nucleoside phosphonates
    Markéta Schinkmanová
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
    Biochem Pharmacol 71:1370-6. 2006
    ..The enzyme does not deaminate AMP and dAMP, or the corresponding nucleosides. It is inhibited by deoxycoformycin 5'-phosphate but not by deoxycoformycin or erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA)...
  51. ncbi request reprint Alpha anomer of 5-aza-2'-deoxycytidine down-regulates hTERT mRNA expression in human leukemia HL-60 cells
    Miroslav Hájek
    Gilead Sciences Research Center, Institute of Organic Chemistry and Biochemistry v v i, AS CR, 166 10 Prague 6, Czech Republic
    Biochem Pharmacol 75:965-72. 2008
    ..Although the primary task of hypomethylating agents in anticancer therapy lies in reactivation of silenced tumour-suppressor genes, the inhibition of hTERT expression might also be a fruitful clinical effect of this approach...
  52. ncbi request reprint Involvement of adenosine A1 receptors in upregulation of nitric oxide by acyclic nucleotide analogues
    Zdenek Zidek
    Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
    Eur J Pharmacol 501:79-86. 2004
    ....
  53. ncbi request reprint Immunobiological activity of N-[2-(phosphonomethoxy)alkyl] derivatives of N6-substituted adenines, and 2,6-diaminopurines
    Zdenek Zidek
    Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
    Eur J Pharmacol 475:149-59. 2003
    ..They exhibit immunostimulatory effects at concentrations as low as 1 to 5 microM. It is suggested that these compounds might be prospective candidates for antiviral therapeutic exploitation...
  54. doi request reprint Inhibition of SAH-hydrolase activity during seed germination leads to deregulation of flowering genes and altered flower morphology in tobacco
    Jaroslav Fulnecek
    Institute of Biophysics, Academy of Sciences of the Czech Republic, vvi, Kralovopolska 135, 612 65 Brno, Czech Republic
    Mol Genet Genomics 285:225-36. 2011
    ..The data further show that plants might be particularly sensitive to accurate setting of SAH/SAM levels during critical developmental periods...
  55. doi request reprint Synthesis of acyclic nucleoside phosphonates
    Antonin Holy
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Curr Protoc Nucleic Acid Chem . 2005
    ..Preparation methods are described in detail for PMEA, PMEG, PMEDAP and its N(6)-cyclopropyl derivative, (R)-PMPA, and (S)-HPMPA, as well as all intermediates and synthons...
  56. pmc Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*
    Gabriel Birkus
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
    Antimicrob Agents Chemother 46:1610-3. 2002
    ..2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively...