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Synthesis of 2’- Hydroxymethyl Cytidine as a Potential Inhibitor for Hepatitis C Virus Polymerase Enzyme

Hamzah, Ali Hayder
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1470333250

Abstract Details

2016, Master of Science, University of Toledo, Medicinal Chemistry.
Hepatitis C virus infection (HCV) is a major cause of liver disease. Due to the asymptomatic nature of the infection, large populations are unware of their infection and become carriers, with progression to chronic stage including liver cirrhosis and hepatocellular carcinoma. Currently, there are seven genotypes and several subtypes of HCV; genotype 1 is the most global distributed form, acquired predominantly through illegal intravenous drug injection. HCV heterogeneity and high replication rates, lead to mutant formation and consequent reinfection. The diseases’ lack of susceptibility to antiviral agents facilitates chronic infection and as such is most challenging when searching for a cure. For decades, the standard of care (SOC) was a combination of PEGylated interferon-a (PEGINF-a) and ribavirin. A Sustained viral response (SVR) was achieved in only a low percentage and was limited to some genotypes and associated with serious adverse effects. It is therefore urgent to develop compounds which have pan-genotype activity, and have increased bioavailability and improved safety profiles. iv A better understanding of the viral life cycle and the determination of the crystal structure of HCV NS5B polymerase enzyme, led to identification of multiple points of intervention to disrupt viral protein synthesis and to interrupt the viral life cycle. Many development stages for these drugs were halted because of either low barrier to resistance or high toxicity. The catalytic site of HCV polymerase is the most conserved motif among HCV and other polymerases and is responsible for HCV RNA replication. It is considered the primary focus in the effort to synthesize molecules targeting the inhibition of HCV life cycle. In our project, we developed a new synthetic pathway toward synthesis of hydroxy methyl cytidine as a potential substrate of the enzyme with an inhibitory effect through working as a chain terminator for nucleotide polymerization.
Amanda Bryant, Freidrich (Advisor)
Biochemistry; Chemistry

Recommended Citations

Citations

  • Hamzah, A. H. (2016). Synthesis of 2’- Hydroxymethyl Cytidine as a Potential Inhibitor for Hepatitis C Virus Polymerase Enzyme [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1470333250

    APA Style (7th edition)

  • Hamzah, Ali. Synthesis of 2’- Hydroxymethyl Cytidine as a Potential Inhibitor for Hepatitis C Virus Polymerase Enzyme. 2016. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1470333250.

    MLA Style (8th edition)

  • Hamzah, Ali. "Synthesis of 2’- Hydroxymethyl Cytidine as a Potential Inhibitor for Hepatitis C Virus Polymerase Enzyme." Master's thesis, University of Toledo, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1470333250

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Toledo and OhioLINK.
Release 3.2.12