Date Approved

10-13-2025

Embargo Period

10-13-2025

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Subash Jonnalagadda, Ph.D.

Committee Member 1

Kandalam Ramanujachary, Ph.D.

Committee Member 2

Omar Tliba, DVM, Ph.D.

Disciplines

Chemistry | Physical Sciences and Mathematics

Abstract

Cancer stem cells (CSC) are cancer cells in a tumor mass that may self-renew and develop into various cell types, resulting in a heterogeneous tumor. CSCs have been shown to have a role in many facets of cancer formation, including tumor genesis, proliferation, and metastatic activity. They are also implicated in chemotherapeutic treatment resistance and the recurrence of some malignancies. Based on these capacities, CSCs have been identified as the next target for cancer therapy and control. Salinomycin's potential for therapeutic use based on ongoing research, as well as the synthesis of its derivatives and their biological activity, will also be emphasized. This study builds upon the established anti-cancer properties of Salinomycin. A library of Salinomycin analogs was synthesized through targeted modifications at two key positions: the C1 carboxylic acid and the C20 hydroxyl. A series of Salinomycin amide derivatives were prepared by replacing the C1 carboxylic acid group with various substituted thiadiazoles and imidazoles. Salinomycin was further derivatized at the C20 position to yield ironomycin. Subsequently, the C20-modified Salinomycin-thiadiazole/imidazole analogs underwent oxidation of the C20 alcohol, followed by amination to generate the corresponding ironomycin analogs. C20 Salinomycin conjugates were also synthesized utilizing the established ironomycin intermediate. The biological activity of these synthesized molecules was evaluated using both in vitro and in vivo assays, demonstrating promising anti-cancer potential.

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