Date of Award
Honors College Thesis
Biological Sciences BS
Matthew Donahue, Ph.D.
Chemistry and Biochemistry
HIV-1 is a retroviral disease that infects CD4+ T cells in the body. Once inside the body, HIV-1 uses human cell machinery to replicate and reproduce using several enzymes to reverse transcribe viral RNA to DNA and integrate the viral DNA into the human genome to reproduce. Several drugs, such as NRTIs, INSTIs, NNRTIs, and PIs, have been created to inhibit specific parts of the viral life cycle and are used in combination to fight HIV-1. However, these medications face challenges of viral mutation and resistance, which increases the importance of creating more potent and effective drugs. Recently, a new class of drugs called ALLINIs have emerged and work by preventing HIV-1 integrase from integrating viral DNA into the host by binding to IN and blocking the IN-LEDGF/p75 binding site on the host. In previous studies, a substituted quinoline further derivatized at position 7 was created and found to be potent in carrying out this action as well as impacting viral maturation via inducing multimerization of IN. In this thesis, a further substituted quinoline structure was synthesized with a R and S enantiomer branching off position 3, where the S form is hypothesized to be more potent in inhibiting HIV-1. A separation attempt was then conducted using a chiral coupling compound. After analysis of the completed reaction by TLC and 1H NMR, the molecule failed to separate into two distinct diastereomers. However, once separated the molecules can be characterized using the Mosher ester model and individually assessed on their multimerization effects on IN to see which diastereomer is more active against HIV-1 and may become a new potent drug in fighting the disease.
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Canfield, Madison, "Separating the R vs. S Enantiomers of a Quinoline Aimed at Inhibiting the Allosteric Binding Pocket of HIV-1 Integrase" (2023). Honors Theses. 917.