C K Chu

Summary

Affiliation: University of Georgia
Country: USA

Publications

  1. ncbi Preclinical investigation of L-FMAU as an anti-hepatitis B virus agent
    C K Chu
    University of Georgia College of Pharmacy, Athens 30602, USA
    Antivir Ther 3:113-21. 1998
  2. ncbi Anti-HIV activity of (-)-(2R,4R)-1- (2-hydroxymethyl-1,3-dioxolan-4-yl)-thymine against drug-resistant HIV-1 mutants and studies of its molecular mechanism
    Chung K Chu
    College of Pharmacy, The University of Georgia, Athens, 30602, USA
    J Med Chem 48:3949-52. 2005
  3. ncbi Antiviral activity of cyclopentenyl nucleosides against orthopox viruses (Smallpox, monkeypox and cowpox)
    C K Chu
    Department of Pharmaceutical and Biomedical Science, College of Pharmacy, The University of Georgia, Athens 30602, USA
    Bioorg Med Chem Lett 13:9-12. 2003
  4. ncbi L-nucleosides: antiviral activity and molecular mechanism
    Giuseppe Gumina
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA
    Curr Top Med Chem 2:1065-86. 2002
  5. ncbi Structure-activity relationships of 2'-fluoro-2',3'-unsaturated D-nucleosides as anti-HIV-1 agents
    Kyeong Lee
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, rdag, Athens, Georgia 30602, USA
    J Med Chem 45:1313-20. 2002
  6. ncbi Antiviral activity of nucleoside analogues against SARS-coronavirus (SARS-coV)
    Chung K Chu
    The University of Georgia, College of Pharmacy, Athens, GA, USA
    Antivir Chem Chemother 17:285-9. 2006
  7. ncbi Synthesis and antiviral activity of oxaselenolane nucleosides
    C K Chu
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 43:3906-12. 2000
  8. ncbi Enantiomeric synthesis of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus
    G Y Song
    College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 44:3985-93. 2001
  9. ncbi Synthesis and potent anti-HIV activity of L-3'-fluoro-2',3'-unsaturated cytidine
    G Gumina
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Org Lett 3:4177-80. 2001
  10. ncbi L-Nucleosides as chemotherapeutic agents
    G Gumina
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA
    FEMS Microbiol Lett 202:9-15. 2001

Research Grants

  1. SYNTHESIS AND BIOTRANSFORMATION OF ANTI-HIV PRODRUGS
    CHUNG CHU; Fiscal Year: 2007
  2. Synthesis/Biological evaluation of Anti-HIV Nucleosides
    David Chu; Fiscal Year: 2005
  3. Carbocyclic Nucleosides for Emerging Viral Diseases
    David Chu; Fiscal Year: 2003
  4. SYNTHESIS AND BIOLOGICAL EVALUATION/ANTIHIV NUCLEOSIDES
    David Chu; Fiscal Year: 2001
  5. SYNTHESIS & BIOLOGICAL EVALUATION OF ANTI-HIV NUCLEOSIDE
    David Chu; Fiscal Year: 1993

Collaborators

Detail Information

Publications74

  1. ncbi Preclinical investigation of L-FMAU as an anti-hepatitis B virus agent
    C K Chu
    University of Georgia College of Pharmacy, Athens 30602, USA
    Antivir Ther 3:113-21. 1998
    ..L-FMAU shows potent anti-HBV activity in vivo against woodchuck hepatitis virus in chronically infected woodchucks and there is no significant virus rebound after cessation of the drug treatment...
  2. ncbi Anti-HIV activity of (-)-(2R,4R)-1- (2-hydroxymethyl-1,3-dioxolan-4-yl)-thymine against drug-resistant HIV-1 mutants and studies of its molecular mechanism
    Chung K Chu
    College of Pharmacy, The University of Georgia, Athens, 30602, USA
    J Med Chem 48:3949-52. 2005
    ..The key reason for this interesting antiviral activity profile is the presence of a dioxolane ring...
  3. ncbi Antiviral activity of cyclopentenyl nucleosides against orthopox viruses (Smallpox, monkeypox and cowpox)
    C K Chu
    Department of Pharmaceutical and Biomedical Science, College of Pharmacy, The University of Georgia, Athens 30602, USA
    Bioorg Med Chem Lett 13:9-12. 2003
    ..Among the synthesized nucleosides, the adenine 2 (Neplanocin A), cytosine 14, and 5-F-cytosine 15 analogues exhibited potent anti-orthopox virus activity, including smallpox virus...
  4. ncbi L-nucleosides: antiviral activity and molecular mechanism
    Giuseppe Gumina
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA
    Curr Top Med Chem 2:1065-86. 2002
    ..This review will discuss the latest advances in L-nucleosides as antiviral agents with a particular focus on the synthesis and molecular mechanism as well as metabolic differences between L- and D-nucleosides...
  5. ncbi Structure-activity relationships of 2'-fluoro-2',3'-unsaturated D-nucleosides as anti-HIV-1 agents
    Kyeong Lee
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, rdag, Athens, Georgia 30602, USA
    J Med Chem 45:1313-20. 2002
    ..The implications for drug resistance of the titled nucleosides with respect to lamivudine-resistant variants (M184V) were also examined, and no significant cross-resistance with the variants was observed with the D-series...
  6. ncbi Antiviral activity of nucleoside analogues against SARS-coronavirus (SARS-coV)
    Chung K Chu
    The University of Georgia, College of Pharmacy, Athens, GA, USA
    Antivir Chem Chemother 17:285-9. 2006
    ..Herein we describe the antiviral activity of several classes of nucleoside analogues evaluated against SARS-CoV in Vero 76 cells, some of which exhibited moderate activity...
  7. ncbi Synthesis and antiviral activity of oxaselenolane nucleosides
    C K Chu
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 43:3906-12. 2000
    ..The results indicate that most of the anti-HIV activity of both cytosine and fluorocytosine nucleosides resides with the (-)-isomers...
  8. ncbi Enantiomeric synthesis of D- and L-cyclopentenyl nucleosides and their antiviral activity against HIV and West Nile virus
    G Y Song
    College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 44:3985-93. 2001
    ..2-3.0 and 15-20 microM, respectively). Among L-(+)-nucleosides, only the cytosine (27) analogue exhibited weak anti-HIV activity (EC(50) 58.9 microM)...
  9. ncbi Synthesis and potent anti-HIV activity of L-3'-fluoro-2',3'-unsaturated cytidine
    G Gumina
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Org Lett 3:4177-80. 2001
    ..L-2',3'-Didehydro-2',3'-dideoxy-3'-fluorocytidine (L-3'-Fd4C), a novel potent anti-HIV agent (EC(50) 0.03 microM in PBM cells), has been synthesized from L-xylose in 14 steps. [reaction: see text]..
  10. ncbi L-Nucleosides as chemotherapeutic agents
    G Gumina
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA
    FEMS Microbiol Lett 202:9-15. 2001
    ..This minireview summarizes some biological features and the current status of these promising L-nucleoside analogues...
  11. ncbi Stereocontrolled syntheses of carbocyclic C-nucleosides and related compounds
    B K Chun
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Org Chem 66:4852-8. 2001
    ....
  12. ncbi Understanding the mode of action of L-nucleosides as antiviral agents: a molecular modeling approach
    K Lee
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, USA
    Nucleosides Nucleotides Nucleic Acids 20:385-8. 2001
    ..Additionally, clinically important M184V mutation, which confers the viral resistance against 3TC and FTC, were studied by the same modeling system...
  13. ncbi Solid phase synthesis of carbocyclic l-2'-deoxynucleosides
    H Choo
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602-2352, USA
    Org Lett 3:1471-3. 2001
    ..The Mitsunobu reaction was used as a condensation method between the carbocyclic moiety and heterocyclic bases. The regioselectivity of the carbocyclic nucleosides was compared between the solid and solution phase syntheses...
  14. ncbi Determination of 3'-azido-2',3'-dideoxyuridine in maternal plasma, amniotic fluid, fetal and placental tissues by high-performance liquid chromatography
    T N Clark
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens 30602-2352, USA
    J Chromatogr B Biomed Sci Appl 755:165-72. 2001
    ..Recoveries ranged from 81 to 96% for AZDU and from 82 to 96% for AZT in the different matrices. Intra-day (n=6) and inter-day (n=9) precision (% RSD) and accuracy (% Error) ranged from 1.48 to 6.25% and from 0.50 to 10.07%, respectively...
  15. ncbi Advances in antiviral agents for hepatitis B virus
    G Gumina
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens
    Antivir Chem Chemother 12:93-117. 2001
    ..This review will summarize the latest advances in anti-HBV therapy, with particular regard to the latest clinical data on the most significant anti-HBV agents. Issues such as viral resistance and combination therapy will be highlighted...
  16. ncbi Synthesis of carbocyclic orotidine analogs as potential orotidine decarboxylase inhibitors
    G Y Song
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens 30602, USA
    Nucleosides Nucleotides Nucleic Acids 20:1915-25. 2001
    ..None of synthesized the compounds inhibited orotidine 5'-monophosphate decarboxylase (EC 4.1.1.23) or orotate phosphoribosyltransferase (EC 2.4.2.10)...
  17. ncbi Practical synthesis of D-cyclopent-2-enone, the key intermediate of carbocyclic nucleosides
    Y H Jin
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602-2352, USA
    Nucleosides Nucleotides Nucleic Acids 22:771-3. 2003
    ..An efficient and practical method for the synthesis of (4R,5R)-4,5-O-isopropylidene-cyclopent-2-enone was developed from D-ribose by using a ring-closing metathesis reaction...
  18. ncbi Molecular mechanism of dioxolane nucleosides against 3TC resistant M184V mutant HIV
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Antiviral Res 63:7-13. 2004
    ....
  19. ncbi Characterization of hepatitis B virus inhibition by novel 2'-fluoro-2',3'-unsaturated beta-D- and L-nucleosides
    S Balakrishna Pai
    Veterans Affairs Medical Center, Decatur, GA, USA
    Antivir Chem Chemother 16:183-92. 2005
    ..This class of nucleosides, which exhibit potent antiviral activity and a favourable safety profile, have potential for the treatment of HBV infections and warrant further development...
  20. ncbi Pharmacology and pharmacokinetics of the antiviral agent beta-D-2',3'-dideoxy-3'-oxa-5-fluorocytidine in cells and rhesus monkeys
    Brenda I Hernandez-Santiago
    Department of Pediatrics, Emory School of Medicine/Veterans Affairs Medical Center, Medical Research 151H, 1670 Clairmont Rd, Decatur, Georgia 30033, SUA
    Antimicrob Agents Chemother 49:2589-97. 2005
    ..These results suggest that further safety and pharmacological studies are warranted to assess the potential of this nucleoside for the treatment of HIV- and HBV-infected individuals...
  21. ncbi Synthesis, antiviral activity, and mechanism of drug resistance of D- and L-2',3'-didehydro-2',3'-dideoxy-2'-fluorocarbocyclic nucleosides
    Jianing Wang
    College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 48:3736-48. 2005
    ..The significant difference of antiviral activity between carbovir and its analogue L-2'F-C-d4G 25 may be due to distortion of the phenyl ring of Tyr115 in the L-2'F-C-d4G-TP/HIV-RT complex, which resulted in a poor pi-pi interaction...
  22. ncbi Mechanism of anti-human immunodeficiency virus activity of beta-D-6-cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine
    Adrian S Ray
    Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520-8066, USA
    Antimicrob Agents Chemother 49:1994-2001. 2005
    ..Poor oral bioavailability observed in rhesus monkeys may be due to the labile glycosidic bond, and special formulation may be necessary for oral delivery...
  23. ncbi In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase
    Urvi M Parikh
    Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Antimicrob Agents Chemother 49:1139-44. 2005
    ..These findings support the inclusion of 3'-azido-3'-deoxythymidine in drug combinations to treat patients having HIV-1(65R) and to prevent its emergence...
  24. ncbi Synthesis, structure-activity relationships, and drug resistance of beta-d-3'-fluoro-2',3'-unsaturated nucleosides as anti-HIV Agents
    Wen Zhou
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 47:3399-408. 2004
    ..Differences between fluorine substitution at the 3' and 2' positions may account for the higher cross-resistance with lamivudine observed in the 2'-fluorinated series...
  25. ncbi Metabolism of the anti-hepatitis C virus nucleoside beta-D-N4-hydroxycytidine in different liver cells
    Brenda I Hernandez-Santiago
    Department of Pediatrics, Emory School of Medicine, and Veterans Affairs Medical Center, Decatur, Georgia 30033, USA
    Antimicrob Agents Chemother 48:4636-42. 2004
    ..Studies using monkey and human whole blood demonstrated more-rapid deamination and oxidation in monkey cells than in human cells, suggesting that NHC may not persist long enough in plasma to be delivered to liver cells...
  26. ncbi Synthesis of 3'-fluoro-2',3'-dideoxy-2',3'-didehydro-4'-ethynyl-D- and -L-furanosyl nucleosides
    Xin Chen
    College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Org Chem 69:6034-41. 2004
    ..All the newly synthesized 4'-substituted nucleosides were tested for their activities against HIV, among which the D-adenine derivative showed moderate anti-HIV activity (EC(50) = 25.1 microM) without significant cytotoxicity...
  27. ncbi In vitro selection and analysis of human immunodeficiency virus type 1 resistant to derivatives of beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine
    Jennifer L Hammond
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA
    Antimicrob Agents Chemother 49:3930-2. 2005
    ..Phenotypic analysis of site-directed mutants defined the role of these mutations in reducing susceptibility to l- or d-d4FC...
  28. ncbi Synthesis and antiviral activity of 7-deazaneplanocin A against orthopoxviruses (vaccinia and cowpox virus)
    Balakumar Arumugham
    University of Georgia College of Pharmacy, Athens, GA 30602, USA
    Bioorg Med Chem Lett 16:285-7. 2006
    ..The synthesized 7-deazaneplanocin A (2) exhibited potent antiviral activity against cowpox and vaccinia viruses without cytotoxicity in HFF cells...
  29. ncbi Pharmacokinetics of the anti-human immunodeficiency virus agent 1-(beta-D-dioxolane)thymine in rhesus monkeys
    Ghazia Asif
    Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
    Antimicrob Agents Chemother 51:2424-9. 2007
    ..The potent antiretroviral activity of D-DOT against a lamivudine- and zidovudine-resistant HIV-1 mutant, together with an excellent pharmacokinetic profile for rhesus monkeys, suggest that further development is warranted...
  30. ncbi Biochemical studies on the mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to 1-(beta-D-dioxolane)thymine triphosphate
    Johan Lennerstrand
    Laboratory of Biochemical Pharmacology, Emory University Veterans Affairs Medical Center, 1670 Clairmont Rd, Medical Research 151 H, Decatur, GA 30033, USA
    Antimicrob Agents Chemother 51:2078-84. 2007
    ....
  31. ncbi D- and L-2',3'-didehydro-2',3'-dideoxy-3'-fluoro-carbocyclic nucleosides: synthesis, anti-HIV activity and mechanism of resistance
    Jianing Wang
    College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 50:1828-39. 2007
    ....
  32. ncbi PAMAM dendrimers and branched polyethyleneglycol (nanoparticles) prodrugs of (-)-beta-D-(2R, 4R)-dioxolane-thymine (DOT) and their anti-HIV activity
    Yuzeng Liang
    The University of Georgia College of Pharmacy, Athens, GA, USA
    Antivir Chem Chemother 17:321-9. 2006
    ..Unfortunately, the PAMAM dendrimers also exhibited increased cytotoxicity. Anti-HIV activity of PEG-DOT conjugates was found to be lower than that of DOT...
  33. ncbi Enantioselective synthesis and antiviral activity of purine and pyrimidine cyclopentenyl C-nucleosides
    Jagadeeshwar R Rao
    The University of Georgia College of Pharmacy, Athens, GA 30602, USA
    Bioorg Med Chem 15:839-46. 2007
    ..Synthesized compounds were evaluated as potential antiviral agents against HIV, SARSCoV, Punta Toro, West Nile, and Cowpox viruses. However, only 9-deazaneplanocin A (1) exhibited moderate anti-HIV activity...
  34. ncbi Synthesis of neplanocin F analogues as potential antiviral agents
    Hongwang Zhang
    The University of Georgia College of Pharmacy, Athens, GA 30602, USA
    Bioorg Med Chem 14:8314-22. 2006
    ..2.1]-hept-5-en-3-one (ABH), was utilized to prepare the target nucleosides. Among the target compounds, 5'-deoxyneplanocin F adenine exhibited moderate anti-HIV activity in human lymphocytes without any marked cytotoxicity...
  35. ncbi Synthesis and anti-HIV activity of D- and L-thietanose nucleosides
    Hyunah Choo
    College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 49:1635-47. 2006
    ....
  36. ncbi Synthesis of cyclopentenyl carbocyclic nucleosides as potential antiviral agents against orthopoxviruses and SARS
    Jong Hyun Cho
    The University of Georgia College of Pharmacy, Athens, GA 30602, USA
    J Med Chem 49:1140-8. 2006
    ..The 1,2,4-triazole analogue (17a) also exhibited moderate antiviral activity (EC(50) 21 microM) against SARSCoV...
  37. ncbi Synthesis and anti-HIV activity of beta-D-3'-azido-2',3'-unsaturated nucleosides and beta-D-3'-azido-3'-deoxyribofuranosylnucleosides
    Srinivas Gadthula
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    Nucleosides Nucleotides Nucleic Acids 24:1707-27. 2005
    ..The resultant protected nucleosides were converted to target nucleosides using appropriate chemical modifications. The final nucleosides were evaluated as potential anti-HIV agents...
  38. ncbi Phosphoramidate and phosphate prodrugs of (-)-beta-D-(2R,4R)-dioxolane-thymine: synthesis, anti-HIV activity and stability studies
    Yuzeng Liang
    The University of Georgia, College of Pharmacy, Athens, GA 30602, USA
    Bioorg Med Chem 14:2178-89. 2006
    ..Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity...
  39. ncbi Synthesis of beta-enantiomers of N4-hydroxy-3'-deoxypyrimidine nucleosides and their evaluation against bovine viral diarrhoea virus and hepatitis C virus in cell culture
    Laurent Hollecker
    Pharmasset Inc, Tucker, GA, USA
    Antivir Chem Chemother 15:43-55. 2004
    ..In conclusion, none of the newly synthesized derivatives exhibited enhanced antiviral activity compared to the parent nucleoside NHC...
  40. ncbi The role of 2',3'-unsaturation on the antiviral activity of anti-HIV nucleosides against 3TC-resistant mutant (M184V)
    Hyunah Choo
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Bioorg Med Chem Lett 13:1993-6. 2003
    ..In 3TC-resistant mutant (M184V) RT, 2'-fluoro-2',3'-unsaturated nucleosides with a bulky 4'-substituent experience significant steric hindrance with the side chain of Val184...
  41. ncbi Probing the mechanistic consequences of 5-fluorine substitution on cytidine nucleotide analogue incorporation by HIV-1 reverse transcriptase
    Adrian S Ray
    Department of Pharmacology, Yale University School of Medicine, New Haven, Conn, USA
    Antivir Chem Chemother 14:115-25. 2003
    ....
  42. ncbi Dynamics of subgenomic hepatitis C virus replicon RNA levels in Huh-7 cells after exposure to nucleoside antimetabolites
    Lieven J Stuyver
    Pharmasset, Inc, Tucker, Georgia 30084, USA
    J Virol 77:10689-94. 2003
    ..cytostasis combined with a sharp decrease in replicon copy number per cell. These results suggest that high levels of CTP and UTP are critical parameters for maintaining the steady-state level replication of HCV replicon in Huh-7 cells...
  43. ncbi Probing the molecular mechanisms of AZT drug resistance mediated by HIV-1 reverse transcriptase using a transient kinetic analysis
    Adrian S Ray
    Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA
    Biochemistry 42:8831-41. 2003
    ..Structure-activity studies of chain terminator removal suggest that analogues that form tight interactions with residues in the RT active site may be more prone to resistance mechanisms mediated by removal...
  44. ncbi l-2',3'-Didehydro-2',3'-dideoxy-3'-fluoronucleosides: synthesis, anti-HIV activity, chemical and enzymatic stability, and mechanism of resistance
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 46:3245-56. 2003
    ..The biological results suggest that, in addition to the sugar conformation, the base moiety may also play a role in their interaction with the M184V RT...
  45. ncbi Synthesis, anti-HIV activity, and molecular mechanism of drug resistance of L-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides
    Hyunah Choo
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 46:389-98. 2003
    ....
  46. ncbi Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture
    Lieven J Stuyver
    Pharmasset Inc, Tucker, Georgia 30084, USA
    Antimicrob Agents Chemother 47:244-54. 2003
    ....
  47. ncbi Antiviral activities and cellular toxicities of modified 2',3'-dideoxy-2',3'-didehydrocytidine analogues
    Lieven J Stuyver
    Veterans Affairs Medical Center and Department of Pediatrics, Emory University School of Medicine, Decatur, Georgia 30033, USA
    Antimicrob Agents Chemother 46:3854-60. 2002
    ..08 micro M) and lamivudine-resistant HIV-1 (EC(90) = 0.15 micro M) is markedly reduced by introduction of a 3'-fluorine in the sugar (EC(90)s of compound 2a, 37.5 and 494 micro M, respectively)...
  48. ncbi Understanding the unique mechanism of L-FMAU (clevudine) against hepatitis B virus: molecular dynamics studies
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Bioorg Med Chem Lett 12:3459-62. 2002
    ....
  49. ncbi Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate
    Adrian S Ray
    Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8066, USA
    Biochemistry 41:5150-62. 2002
    ..This compound shows promise as a potent antiviral especially with the drug resistant M184V HIV-1 RT that is so often encountered in a clinical setting...
  50. ncbi Stereoselective synthesis and antiviral activity of D-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thionucleosides
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 45:4888-98. 2002
    ....
  51. ncbi Molecular mechanism of DApd/DXG against zidovudine- and lamivudine- drug resistant mutants: a molecular modelling approach
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, USA
    Antivir Chem Chemother 13:115-28. 2002
    ..The enzyme-inhibitor complexes with good binding affinity showed tight binding modes by closing the gap between the two domains, whereas weak inhibitors gave open and loose complexes...
  52. ncbi 2'-Fluoro-4'-thio-2',3'-unsaturated nucleosides: anti-HIV activity, resistance profile, and molecular modeling studies
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    Nucleosides Nucleotides Nucleic Acids 22:611-5. 2003
    ..Molecular modeling studies revealed that the unnatural sugar moiety of the L-nucleosides as well as 4'-sulfur atom of the D-isomer has a steric conflict with the bulky side chain of valine 184, resulting in cross-resistance...
  53. ncbi Synthesis, structure-activity relationships, and mechanism of drug resistance of D- and L-beta-3'-fluoro-2',3'-unsaturated-4'-thionucleosides as anti-HIV agents
    Wei Zhu
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 47:1631-40. 2004
    ..Like other unnatural L-nucleosides, the unfavorable steric hindrance of the sugar moiety of L-3'F-4'Sd4CTP with the side chain of Val184 explains its significant cross-resistance to the M184V mutant...
  54. ncbi Mechanism of antiviral activities of 3'-substituted L-nucleosides against 3TC-resistant HBV polymerase: a molecular modelling approach
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, USA
    Antivir Chem Chemother 14:309-19. 2003
    ....
  55. ncbi Understanding the molecular mechanism of drug resistance of anti-HIV nucleosides by molecular modeling
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Front Biosci 9:164-86. 2004
    ....
  56. ncbi Synthesis and potent anti-HIV activity of L-2',3'-didehydro-2',3'-dideoxy-2'-fluoro-4'-thiocytidine
    Yongseok Choi
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    Org Lett 4:305-7. 2002
    ..The synthesized compound 11 shows potent antiviral activity against HIV-1...
  57. ncbi Novel use of a guanosine prodrug approach to convert 2',3'-didehydro-2',3'-dideoxyguanosine into a viable antiviral agent
    Adrian S Ray
    Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA
    Antimicrob Agents Chemother 46:887-91. 2002
    ..In addition, cyclo-D4G had increased stability, lipophilicity, and solubility, as well as decreased toxicity relative to D4G, suggesting that further study is warranted...
  58. ncbi Practical synthesis of D- and l-2-cyclopentenone and their utility for the synthesis of carbocyclic antiviral nucleosides against orthopox viruses (smallpox, monkeypox, and cowpox virus)
    Yun H Jin
    College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    J Org Chem 68:9012-8. 2003
    ..Preliminary antiviral activity against orthopox viruses (smallpox, monkeypox, and cowpox virus) of the synthesized nucleosides are described...
  59. ncbi Studies of molecular mechanism of tenofovir against 3TC- and AZT-resistance mutant HIV-1 reverse transcriptase
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Bioorg Med Chem Lett 13:4019-22. 2003
    ..TFV-DP is located far away from the bulky side chain of Val184 in M184V RT and tenofovir is readily translocated without steric hindrance with Asp185 after incorporation into the growing primer chain complexed with AZT-resistant RT...
  60. ncbi Synthesis, biological evaluation and molecular modeling studies of N6-benzyladenosine analogues as potential anti-toxoplasma agents
    Young Ah Kim
    University of Georgia College of Pharmacy, Athens, GA 30602, USA
    Biochem Pharmacol 73:1558-72. 2007
    ..gondii adenosine kinase by induced fit molecular modeling...
  61. ncbi In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs
    Marco Radi
    The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA
    J Med Chem 50:2249-53. 2007
    ..These in vitro results suggest that the in vivo therapeutic efficacy of l-1,3-dioxolane-cytidine against solid tumors may be improved with prodrug strategies...
  62. ncbi Synthesis and anti-HIV activity of (-)-beta-D-(2R,4R)-1,3-dioxolane-2,6-diamino purine (DAPD) (amdoxovir) and (-)-beta-D-(2R,4R)-1,3-dioxolane guanosine (DXG) prodrugs
    Janarthanan Narayanasamy
    The University of Georgia College of Pharmacy, Athens, GA 30602, United States
    Antiviral Res 75:198-209. 2007
    ..5'-L-Valyl DAPD 20 and organic acid salts 21-24 also exhibited enhanced anti-HIV activity in comparison to DAPD, while DXG prodrugs 16 and 17 exhibited lower potency than that of DXG or DAPD...
  63. ncbi Structure-activity relationships of 7-deaza-6-benzylthioinosine analogues as ligands of Toxoplasma gondii adenosine kinase
    Young Ah Kim
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 51:3934-45. 2008
    ..The most potent compounds, 7-deaza- p-cyano-6-benzylthioinosine (IC 50 = 5.3 microM) and 7-deaza- p-methoxy-6-benzylthioinosine (IC 50 = 4.6 microM), were evaluated in cell culture to delineate their selective toxicity...
  64. ncbi Efficient synthesis of 2-deoxy-L-erythro-pentose (2-deoxy-L-ribose) from L-arabinose
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, Center for Drug Discovery, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Carbohydr Res 337:397-402. 2002
    ..The radical precursor, a phenoxythiocarbonyl ester, was prepared in situ, and the most efficient deoxygenation was achieved by slow addition of tributyltin hydride to the reaction mixture...
  65. ncbi Synthesis and in vitro anti-HCV activity of beta-D- and 1-2'-deoxy-2'-fluororibonucleosides
    Junxing Shi
    Pharmasset, Inc, Tucker, GA, USA
    Nucleosides Nucleotides Nucleic Acids 24:875-9. 2005
    ..All the L-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot reliably predict anti-HCV activity in vitro...
  66. ncbi Cell line dependency for antiviral activity and in vivo efficacy of N-methanocarbathymidine against orthopoxvirus infections in mice
    Donald F Smee
    Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322 5600, USA
    Antiviral Res 73:69-77. 2007
    ..Cidofovir (100mg/kg/day) protected animals from death in all three infections...
  67. ncbi Synthesis, biological activity and molecular modeling of 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase
    Vikas Yadav
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2352, USA
    J Med Chem 47:1987-96. 2004
    ....
  68. ncbi Simultaneous determination of 3'-azido-2',3'-dideoxyuridine and novel prodrugs in rat plasma by liquid chromatography
    Linghui Kong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2352, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 795:371-6. 2003
    ..5 microg/ml for prodrug I. The intra- and inter-day variations were less than 10% and accuracies were greater than 90%. This method is rapid, sensitive and reproducible for the determination of AZDU and prodrugs in rat plasma...
  69. ncbi Pharmacokinetics of the antiviral agent beta-L-3'-fluoro-2',3'-didehydro-2',3'-dideoxycytidine in rhesus monkeys
    Ghazia Asif
    Department of Pediatrics, Emory University, Atlanta, Georgia, USA
    Antimicrob Agents Chemother 49:560-4. 2005
    ..49), suggesting that further development of this compound may warrant other approaches, such as development of a prodrug to improve its oral absorption...
  70. ncbi Pharmacokinetic evaluation of 3'-azido-2', 3'-dideoxyuridine-5'-O-valinate-hydrochloride as a prodrug of the anti-HIV nucleoside 3'-azido-2', 3'-dideoxyuridine
    Linghui Kong
    Forest Laboratories, Inc, Jersey City, NJ, USA
    Antivir Chem Chemother 14:263-70. 2003
    ..Prodrug AZDU-VAL demonstrated improved oral bioavailability as evidenced by complete absorption and efficient bioconversion to AZDU. The results suggest that AZDU-VAL may be a promising prodrug for the delivery of AZDU...
  71. ncbi Effects of fluorine substitution of cytosine analogues on the binding affinity to HIV-1 reverse transcriptase
    Youhoon Chong
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Bioorg Med Chem Lett 14:437-40. 2004
    ....
  72. ncbi Molecular mechanisms of adefovir sensitivity and resistance in HBV polymerase mutants: a molecular dynamics study
    Vikas Yadav
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
    Bioorg Med Chem Lett 14:4313-7. 2004
    ....
  73. ncbi Synthesis of novel spiro[2.3]hexane carbocyclic nucleosides via enzymatic resolution
    Lavanya Bondada
    Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA
    Org Lett 6:2531-4. 2004
    ..Acetate 3 and (-)-acetate 14 were converted to R- and S-9-(6-hydroxymethylspiro[2.3]hexane)-4-adenine, respectively...
  74. ncbi 7-Deaza-6-benzylthioinosine analogues as subversive substrate of Toxoplasma gondii adenosine kinase: activities and selective toxicities
    Omar N Al Safarjalani
    Department of Pharmacology and Toxicology, Center for AIDS Research, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Biochem Pharmacol 76:958-66. 2008
    ..3 microM). These results further confirm that T. gondii adenosine kinase is an excellent target for chemotherapy and that 7-deaza-6-benzylthioinosines are potential antitoxoplasmic agents...

Research Grants17

  1. SYNTHESIS AND BIOTRANSFORMATION OF ANTI-HIV PRODRUGS
    CHUNG CHU; Fiscal Year: 2007
    ..If any prodrugs are found to be promising during these studies, we plan to advance them as clinical candidates. ..
  2. Synthesis/Biological evaluation of Anti-HIV Nucleosides
    David Chu; Fiscal Year: 2005
    ..This is the first such studies demonstrating the potential of this molecular modeling approach. ..
  3. Carbocyclic Nucleosides for Emerging Viral Diseases
    David Chu; Fiscal Year: 2003
    ..We will also send the proposed compounds for antiviral evaluation against Hanta virus and other emerging virus if the screening systems become available in our collaborator's laboratories. ..
  4. SYNTHESIS AND BIOLOGICAL EVALUATION/ANTIHIV NUCLEOSIDES
    David Chu; Fiscal Year: 2001
    ....
  5. SYNTHESIS & BIOLOGICAL EVALUATION OF ANTI-HIV NUCLEOSIDE
    David Chu; Fiscal Year: 1993
    ..Additionally, the proposed compounds will also be evaluated in other anti-viral screening systems including HCMV, herpes, RSV, human hepatitis B virus...