Date of Award

2022-12-01

Degree Name

Doctor of Philosophy

Department

Biological Sciences

Advisor(s)

Renato J. Aguilera

Abstract

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule organization. Additionally, structural analysis and medical text mining revealed a functional relationship between Tpz-1 and the understudied thienopyrazole chemical group. This dissertation therefore offers our colleagues in anticancer drug discovery an innovative methodology and class of molecules to drive future small molecule screening initiatives.

Language

en

Provenance

Received from ProQuest

File Size

185 p.

File Format

application/pdf

Rights Holder

Jessica Dyanne Hess

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