Dissertations, Theses, and Capstone Projects
Date of Degree
6-2024
Document Type
Dissertation
Degree Name
Ph.D.
Program
Biochemistry
Advisor
Maria Contel
Committee Members
Lesley Davenport
Brian Gibney
Sanjai Pathak
Joe Ramos
Subject Categories
Biochemistry | Biology | Chemistry | Computational Chemistry | Inorganic Chemistry | Medicinal-Pharmaceutical Chemistry | Organic Chemistry
Keywords
heterometallic, platinum(IV), gold(I), anticancer agents, TNBC
Abstract
Heterometallic compounds have emerged as prospective multitarget anticancer drugs. These species may display improved efficacy and physicochemical properties compared to the individual metallic fragments, while helping combat drug resistance by exerting effects on multiple pathways. In this thesis we describe the synthesis of new bi- and tri-metallic compounds based on platinum(IV) compounds containing FDA-approved platinum agents, and gold(I) derivatives with known anticancer properties. We demonstrate their toxicity and selectivity against a small panel of renal, bladder, ovarian, and breast cancer cell lines, as well as their synergistic effects. We have selected a trinuclear PtAu2compound containing the Pt(IV) core based on oxaliplatin for further investigation for its cell-death pathway, cell and organelle uptake and anticancer effects against the triple-negative breast cancer (TNBC) MDA-MB-231 cell line. This compound induces apoptosis and accumulates mainly in the nucleus and mitochondria. It also exerts remarkable antimigratory and antiangiogenic properties and has a potent cytotoxic effect against TNBC 3D spheroids. Trinuclear compounds do not seem to display relevant interactions with calf thymus (CT) DNA and plasmid (pBR322) even in the presence of reducing agents but inhibit pro-angiogenic enzyme thioredoxin reductase (TrxR) in TNBC cells. These results highlight the potential of heterometallic Pt-Au compounds as anticancer agents for TNBC and other cancers.
Recommended Citation
Lopez-Hernandez, Javier E., "Development of Platinum(IV)-Gold(I)-Based Anticancer Agents" (2024). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/5720
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Biochemistry Commons, Biology Commons, Computational Chemistry Commons, Inorganic Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons