Date of Award
Doctor of Philosophy (PhD)
John K. Buolamwini, Ph.D.
Peter K. Bridson, Ph.D. Isaac O. Donkor, Ph.D. Duane D. Miller, Ph.D. Bob M. Moore, Ph.D.
Using prior biological data, pharmacophore models were made for hCNT1, hCNT3, hENT1, and hENT4. The hCNT3 and hCNT1 pharmacophore were used to select compounds for biological testing. The NBMPR analogue and dipyridamole analogue hENT1 pharmacophores were compared to each other and to a combined pharmacophore for hENT1. The dipyridamole analogue pharmacophore better predicted non-nucleoside small molecule inhibitors, and as such appears to be the better tool for aiding in the design of new small molecule inhibitors. The hCNT3 pharmacophore failed to select active compounds and as such must be redesigned. The hCNT1 pharmacophore succeeded in identifying two moderately active compounds and when the hits were added into the data set to make a new pharmacophore, a more statistically valid model was achieved. The hCNT1 model is a statistically valid model for in silico screening of compounds.
Playa, Hilaire Colleen , "Computer-Aided Drug Design and Discovery, Screening and Synthesis of Small Molecule Inhibitors of Nucleoside Transporters" (2014). Theses and Dissertations (ETD). Paper 398. http://dx.doi.org/10.21007/etd.cghs.2014.0247.