The main objective of this research is to synthesize and characterize carbocyclic nucleosides that can be used in the treatment of viral infectious diseases, specifically hepatitis B (HBV) and hepatitis C (HCV). We plan to synthesize a novel class of nucleosides and investigate their antiviral properties in an effort to discover analogs with increased potency, reduced cytotoxicity, and greater metabolic stability. Specifically, we aim to synthesize a number of carbocyclic analogs of a naturally occurring nucleoside, formycin. The proposed compounds are designed to systematically combine structural features of two known classes of antiviral compounds. The target compounds will be synthesized and purified by standard separation techniques and then characterized by using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared spectroscopy etc. Antiviral assays of the target compounds will be conducted to investigate their activity against hepatitis B and hepatitis C viruses. In future projects, the target compounds and many more analogs will be tested to determine their biological activities against a wide range of viruses. Project Narrative/Relevance Viral infectious diseases (including Hepatitis B and Hepatitis C) are one of the areas of public health where significant health disparity is seen. The serious limitations of the current therapeutic interventions call for the development of new agents. This proposal is designed to address this need by synthesizing a new class of carbocyclic nucleosides as antiviral agents. Carbocyclic nucleosides are finding increased application in the treatment of viral infectious diseases such as Human Immunodeficiency Virus (HIV, AIDS), Hepatitis B virus and the Herpes viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Pilot Research Project (SC2)
Project #
5SC2AI083926-02
Application #
7753225
Study Section
Special Emphasis Panel (ZGM1-MBRS-X (CH))
Program Officer
Koshy, Rajen
Project Start
2009-01-01
Project End
2011-12-31
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
2
Fiscal Year
2010
Total Cost
$114,304
Indirect Cost
Name
Elizabeth City State University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
066024357
City
Elizabeth City
State
NC
Country
United States
Zip Code
27909
Bazile, Quachel; Serbessa, Tesfaye; Zhong, Junyan (2012) An efficient synthesis of the 4'-epimer of 2-fluoronoraristeromycin. Tetrahedron Lett 53:1435-1437
Hinton, Shante; Riddick, Alecia; Serbessa, Tesfaye (2012) Deoxy Derivatives of L-like 5'-Noraristeromycin. Tetrahedron Lett 53:1753-1755
Yu, Henry; Serbessa, Tesfaye (2010) N-6 Substituted Deoxygenated Derivatives of L-like 5'-Noraristeromycin. Bull Chem Soc Ethiop 24:439-446