Design, Synthesis, and Characterization of HDAC Inhibitors as Coordination Ligands for Platinum
Poster Number
19A
Research or Creativity Area
Natural Sciences
Abstract
Since the accidental discovery of the first platinum-containing drug, cisplatin, this family of complexes has become widely used in medicine to effectively eradicate further proliferation of uncontrolled somatic cell division through apoptosis. To enhance the efficiency and selectivity toward cancer cells, combination therapy regarding histone deacetylase inhibitors (HDACi) and Pt have been considered as one of the new directions for cancer therapy. With the exploration of developing drugs that inhibit histone deacetylases, the synergistic effects of HDAC inhibitors and platinum compounds have led to promising results. By combining both agents, HDAC inhibitors prevent the deacetylation of the chromatin structure leaving chromatin in a euchromatin state which leads to the upregulation of pro-apoptotic genes and induces cell death. At the same time, HDAC inhibitors impair DNA repair mechanisms within cancer cells, allowing platinum to bind to the DNA and effectively induce cytotoxic effects on cancerous DNA. In this project, two HDAC inhibitors with monodentate (L17) and bidentate coordination site (L21) were designed and synthesized. TLC, MS, and NMR are conducted for structural characterization and purity verification of each precursor and final product.
Location
Don and Karen DeRosa University Center (DUC) Poster Hall
Start Date
27-4-2024 10:30 AM
End Date
27-4-2024 12:30 PM
Design, Synthesis, and Characterization of HDAC Inhibitors as Coordination Ligands for Platinum
Don and Karen DeRosa University Center (DUC) Poster Hall
Since the accidental discovery of the first platinum-containing drug, cisplatin, this family of complexes has become widely used in medicine to effectively eradicate further proliferation of uncontrolled somatic cell division through apoptosis. To enhance the efficiency and selectivity toward cancer cells, combination therapy regarding histone deacetylase inhibitors (HDACi) and Pt have been considered as one of the new directions for cancer therapy. With the exploration of developing drugs that inhibit histone deacetylases, the synergistic effects of HDAC inhibitors and platinum compounds have led to promising results. By combining both agents, HDAC inhibitors prevent the deacetylation of the chromatin structure leaving chromatin in a euchromatin state which leads to the upregulation of pro-apoptotic genes and induces cell death. At the same time, HDAC inhibitors impair DNA repair mechanisms within cancer cells, allowing platinum to bind to the DNA and effectively induce cytotoxic effects on cancerous DNA. In this project, two HDAC inhibitors with monodentate (L17) and bidentate coordination site (L21) were designed and synthesized. TLC, MS, and NMR are conducted for structural characterization and purity verification of each precursor and final product.
