Sarah Tilley, Karla Leonard, Justine Garcia and Dr. Ahmed Awad
Pancreatic cancer, specifically Pancreatic Ductal Adenocarcinoma (PDAC) has posed a multitude of difficulties for researchers and medical doctors alike. PDAC is difficult to detect, and oftentimes goes unnoticed until standard treatments such as surgery are not feasible or simply too risky. The leading treatment for pancreatic cancer, gemcitabine, has many issues associated with delivery due to the hydrophilic nature of the two fluorines located on the 2’ Carbon of the ribose. Furthermore, when gemcitabine enters the cell, the nitrogenous portion of this cytidine nucleoside is often deaminated into uracil by cytidine deaminase which results in the exportation of the molecule out of the cell before it can reach the target protein, ribonucleotide reductase (RNR). To increase the efficacy of such molecules towards RNR, a series of novel nucleoside analogues modified at the 2’ region of the ribose. These modifications include sulfamoyl functional groups to increase stability by hydrogen bonding to key amino acid residues, A605, T607, and S202 found in RNR. Molecular docking studies demonstrated that these novel molecules have higher binding affinity to the target enzyme, are capable of forming more hydrogen bonds, and in fact bind to these important residues found in the catalytic site of RNR. Furthermore, analysis through ADME and PASS predictions have shed more light on the potential of these novel nucleoside analogs as cancer therapeutics.
Session 2 – 3:00p.m. – 4:15p.m.
Room D – Sierra 2422