Amy Bowman

An important enzyme that catalyzes the rate-limiting step in de novo synthesis of guanosine nucleotides is inosine-5’-monophosphate (IMPDH2). The type II isoform of IMPDH2 is widely known to be linked to malignant transformation and thus, have implications in cellular proliferation. The gene expression of this dehydrogenase has been upregulated in cancerous tissue when compared to normal tissue. The first discovered inhibitor of IMPDH2 is mycophenolic acid (MPA). MMF (mycophenolate mofetil), an MPA prodrug, is an FDA approved drug used for the prevention of graft rejection during organ transplants and has recently been shown to have anticancer properties. MPA has exhibited the promotion of apoptosis in cancer cells in previous studies, leading to further investigations of this compound’s anti-cancer properties. A major drawback of MPA is that it has low oral bioavailability. In this regard, highly water-soluble amides have been synthesized. To synthesize an amide complex from MPA, organic amines have been coupled to the acid that increases its bioavailability and solubility. To assess the cytotoxicity of the synthesized compounds, an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay has been carried out in vitro on a wide range of cancer cell lines such as 4T1, MDA-MB-231, MCF7, WiDr, and MiaPaCa-2.