Synthesis and Characterization of HDACi Derivatives and Pt Complexes
Poster Number
22C
Format
Poster Presentation
Faculty Mentor Name
Qinliang Zhao
Faculty Mentor Department
Chemistry
Graduate Student Mentor Name
Brenda Sanchez
Graduate Student Mentor Department
Chemistry
Abstract/Artist Statement
Histone deacetylase (HDAC) enzymes are overexpressed in several types of cancer cells, leading to the application of HDAC inhibitors (HDACi), such as vorinostat, as anticancer agents. This research aims to create bifunctional anticancer drugs by the combination of vorinostat derivatives with platinum metal centers, forming Pt(II) and Pt(IV) complexes with enhanced selectivity and cytotoxicity towards cancer cells. The HDACi derivatives have the general structure of a surface recognition domain cap to locate an HDAC enzyme, a linker in the center, and a hydroxamic acid to bind to and inhibit the active zinc site of the enzyme. The HDACi derivatives 17 and 30 similarly have a phenyl cap connected to a 6-carbon linker, followed by a hydroxamic acid. The cap domains of both derivatives have an ethylenediamine or o-phenylenediamine group as bidentate ligands when binding to the platinum center. Synthesis of the derivatives starts with a nucleophilic substitution reaction to combine the cap and linker, an imine formation and reduction to attach a diamine, one of which is Boc-protected. Formation of the hydroxamic acid through aminolysis and deprotection of the amine group on the cap resulted in the final product. Synthesis of Pt(II) complex involved the ligand substitution reaction of potassium tetrachloroplatinate (II) with ethylenediamine in water for several hours, yielding Pt(Cl2)(en). The Pt(IV) complex is subsequently produced from oxidation of the Pt(II) complex by hydrogen peroxide, forming Pt(Cl)2(en)(OH)2. Intermediates and products from HDACi synthesis and metal chemistry were characterized by NMR spectroscopy and Mass Spectrometry.
Location
Information Commons, William Knox Holt Memorial Library and Learning Center
Start Date
29-4-2023 10:00 AM
End Date
29-4-2023 1:00 PM
Synthesis and Characterization of HDACi Derivatives and Pt Complexes
Information Commons, William Knox Holt Memorial Library and Learning Center
Histone deacetylase (HDAC) enzymes are overexpressed in several types of cancer cells, leading to the application of HDAC inhibitors (HDACi), such as vorinostat, as anticancer agents. This research aims to create bifunctional anticancer drugs by the combination of vorinostat derivatives with platinum metal centers, forming Pt(II) and Pt(IV) complexes with enhanced selectivity and cytotoxicity towards cancer cells. The HDACi derivatives have the general structure of a surface recognition domain cap to locate an HDAC enzyme, a linker in the center, and a hydroxamic acid to bind to and inhibit the active zinc site of the enzyme. The HDACi derivatives 17 and 30 similarly have a phenyl cap connected to a 6-carbon linker, followed by a hydroxamic acid. The cap domains of both derivatives have an ethylenediamine or o-phenylenediamine group as bidentate ligands when binding to the platinum center. Synthesis of the derivatives starts with a nucleophilic substitution reaction to combine the cap and linker, an imine formation and reduction to attach a diamine, one of which is Boc-protected. Formation of the hydroxamic acid through aminolysis and deprotection of the amine group on the cap resulted in the final product. Synthesis of Pt(II) complex involved the ligand substitution reaction of potassium tetrachloroplatinate (II) with ethylenediamine in water for several hours, yielding Pt(Cl2)(en). The Pt(IV) complex is subsequently produced from oxidation of the Pt(II) complex by hydrogen peroxide, forming Pt(Cl)2(en)(OH)2. Intermediates and products from HDACi synthesis and metal chemistry were characterized by NMR spectroscopy and Mass Spectrometry.