Keywords
Small Cell Lung Carcinoma; Medicinal Chemistry, SDHi, SCLC, Organic Synthesis, Drug Development
Abstract
The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By blocking the binding of ubiquinone, the succinate dehydrogenase complex is inhibited, and succinate levels rise, damaging the metabolic homeostasis of the tumor cells. In turn, these cells slow in proliferation. With the support of cancer therapeutics, once rapidly developing tumors can be suppressed with the hopes of providing cancer remission. This paper publishes the effective synthesis and characteristics of these drugs. The H2/Z14 (Molecular weight of 308.39) synthetic route was partially synthesized to the 1,2,4-oxadiazole through two steps of amidoxime formation under mildly basic conditions and cyclization under mildly acidic conditions. C6/Z96 (Molecular weight of 369.73) was produced through a two-step scheme of nitrile substitution under mildly basic conditions and nucleophilic aromatic substitution under strongly acidic conditions. C6/Z96 was ultimately purified by recrystallization, and successful synthesis in both schemes were verified through analytical CNMR, HNMR, LC-MS, and IR diagnostic techniques.
Thesis Completion Year
2026
Thesis Completion Semester
Summer
Thesis Chair
Yuan, Yu
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Thesis Discipline
Medicinal Chemistry
Language
English
Access Status
Open Access
Length of Campus Access
None
Campus Location
Orlando (Main) Campus
STARS Citation
Graves, Lauren M., "Synthesis and Characterization of Succinate Dehydrogenase Inhibitors H2/Z14 and C6/Z96 in Order to Combat Small Cell Lung Cancer" (2026). Honors Undergraduate Theses. 677.
https://stars.library.ucf.edu/hut2024/677
Included in
Cancer Biology Commons, Heterocyclic Compounds Commons, Internal Medicine Commons, Medicinal and Pharmaceutical Chemistry Commons, Natural Products Chemistry and Pharmacognosy Commons, Organic Chemicals Commons, Organic Chemistry Commons, Other Chemicals and Drugs Commons, Pharmaceutical Preparations Commons, Pharmaceutics and Drug Design Commons, Respiratory Tract Diseases Commons
Accessibility Statement
This item was created or digitized prior to April 24, 2027, or is a reproduction of legacy media created before that date. It is preserved in its original, unmodified state specifically for research, reference, or historical recordkeeping. In accordance with the ADA Title II Final Rule, the University Libraries provides accessible versions of archival materials upon request. To request an accommodation for this item, please submit an accessibility request form.