Scholar: Alexandra Pearce
Major: Mathematics and Profesional Chemistry
Faculty Mentors: Dr. Thomas Bell
Research Topic: Synthesis of Macrocyclic Polyamines and Their Metal Complexes Targeting HIV-1
Abstract: M40401, a macrocyclic polyamine, is a well-known antioxidant and, as of late, it has been studied for anti-HIV properties. It was reported to reduce apoptosis of astrocytes caused by HIV-1 infected macrophages (M/M) supernatants(1), and in 2005, a poster presented by Stefano Aquaro at the International Conference for Antiviral Research claimed that HIV-1 replication was reduced in infected M/M when treated with M40401. Our goal is to synthesize M40403, a similar molecule, as well as other related molecules for further study. This will be accomplished by first synthesizing N,N'-Bis[(1R,2R)-(2-amino)cyclohexyl]-1,2-diaminoethane tetrachloride, and manganese chloride from 1,2-diaminocyclohexane. Then this compound will undergo metal-templated condensation with an existing head group and metal to create a Schiff's base, which will then be reduced. M40403 and previously synthesized related molecules have been shown to have anti-HIV properties; in particular, these molecules appear to act as HIV-1 entry-inhibitors by down-modulating the CXCR4 and CCR5 co-receptors found on T-cells. We will synthesize at least three more related molecules in an attempt to maximize the ratio of potency to toxicity. Promising IC50 values have already been reported against HIV-1 for some of the related molecules. Hopefully by tweaking the molecules, we will find one that can eventually be made into a drug to help the fight against HIV-1.
1. Mollace, V.; Salvemini, D.; Riley, D. P.; Muscoli, C.; Iannone, M.; Granato, T.; "The contribution of oxidative stress in apoptosis of human cultured astroglial cells induced by supernatants of HIV-1-infected macrophages," J. Leukoc. Biol. 2002, 71, 65-72.
New Scholar: 2011 cohort
Graduated With Baccalaureate Degree: 2012