Computer-Aided Drug Design and Discovery, Screening and Synthesis of Small Molecule Inhibitors of Nucleoside Transporters

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Pharmaceutical Sciences

Year dc:date.available

2014

Author dc:creator

• Playa, Hilaire Colleen

Contributors dc:contributor

• John K. Buolamwini, Ph.D.

• SLC29
• nucleoside transporters
• nucleosides
• PMAT
• QSAR
• SLC28
• Medicinal and Pharmaceutical Chemistry
• Medicine and Health Sciences
• Pharmaceutics and Drug Design
• Pharmacy and Pharmaceutical Sciences

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/398

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1397