Mohsan Chaudhry, Chemistry and Biochemistry
“Ring-Expanded Nucleotides/Nucleotides as Potential Anti-Viral and Anti-Cancer Agents”
Faculty Mentor: Dr. Ramachandra Hosmane
Expected Graduation Date: May 2011
Cancer and viral infection are the predominant factors for the high mortality rates. A number of ring-expanded nucleosides (RENs) and nucleotides (RENTs) have been reported to be highly active against a wide variety of tumor and viral cell lines. RENs/RENTs are a rich source of inhibitors of the enzymes in purine metabolism, and of those utilizing ATP/GTP either as energy cofactors or as nucleic acid building blocks. Most RENs/RENTs synthesized and screened thus far are planar, aromatic compounds. My project explores the effect of non-planar RENs/RENTs on the biological activity. We hypothesize that the non-planar inhibitors will better mimic the transition states of the relevant enzyme catalyzed reactions and therefore, would act as better inhibitors. My project is aimed at synthesizing the appropriate heterocyclic precursors to the ultimate target RENs/RENTs. The synthesis of the target structure starts with the commercially available 4-Nitroimidazole followed by introduction and hydrolysis of the acetal group to form an aldehyde, reduction of the nitro group to an amino group, followed by ring closure. The final reduction of the imino into an amino group will afford the target ring system.