Design And Synthesis Of Therapeutic Molecules Targeted At Metabolic Pathways Of Cancer And Lipid Signaling In Fungal Diseases

Author

Jennifer Uzoamaka Nnaemeka, Prairie View A&M University

Date of Award

12-2024

Document Type

Thesis

Degree Name

Master of Science

Degree Discipline

Chemistry

Abstract

Cancer remains a leading cause of global mortality, with 20 million new cases and 9.7 million deaths recorded in 2022 (WHO, 2024). While advancements like nanoparticles and monoclonal antibodies offer new treatments, they often cause severe toxicity to normal cells. This study introduced novel thiamin-based compounds targeting enzymes critical for cancer cell proliferation. These compounds were synthesized via a three-step process involving tosylation, SN2 coupling with phenolic compounds, and subsequent reactions to form thiamin-like-phenol derivatives. Yields ranged from 50-70%, and Nuclear Magnetic Resonance (NMR) confirmed their structures. Anticancer activity was assessed by the National Cancer Institute. Separately, drug-resistant fungal infections, particularly from Candida glabrata, are a growing public health concern. This study addressed this issue by targeting Sec14 lipid-binding proteins, essential for lipid signaling, using small molecule inhibitors (SMIs) derived from piperazine. Results suggest Sec14 inhibition as a promising approach for developing next-generation antifungal therapies. In summary, this thesis presents two projects: synthesizing thiamine-phenol derivatives for cancer treatment and exploring SMIs as potential antifungal agents against C. glabrata.

Keywords: Cancer, phenols, Thiamin, drug resistance, piperazine, NMR.

Committee Chair/Advisor

Sameh Abdelwahed

Committee Member

Ananda Amarasekara

Committee Member

Neelgund Gururaj

Committee Member

Yunxiang Gao

Publisher

Prairie View A&M University

Rights

© 2021 Prairie View A & M University

Date of Digitization

1/08/2025

Contributing Institution

John B Coleman Library

City of Publication

Prairie View

MIME Type

Application/PDF

Recommended Citation

Nnaemeka, J. U. (2024). Design And Synthesis Of Therapeutic Molecules Targeted At Metabolic Pathways Of Cancer And Lipid Signaling In Fungal Diseases. Retrieved from https://digitalcommons.pvamu.edu/pvamu-theses/1541