Design, Synthesis, and Characterization of HDAC Inhibitors as Coordination Ligands for Platinum

Lead Author Affiliation

Biochem

Lead Author Status

Undergraduate - Junior

Second Author Affiliation

Biochem

Second Author Status

Undergraduate - Junior

Third Author Affiliation

Pre-Dental

Third Author Status

Undergraduate - Sophomore

Fourth Author Affiliation

Pre-Dental

Fourth Author Status

Undergraduate - Sophomore

Fifth Author Affiliation

Pre-Dental

Fifth Author Status

Undergraduate - Junior

Sixth Author Affiliation

Chemistry

Sixth Author Status

Faculty Mentor

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.

This document is currently not available here.

Share

COinS
 

Design, Synthesis, and Characterization of HDAC Inhibitors as Coordination Ligands for Platinum

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.