Design, Synthesis, and Characterization of a HDACi to coordinate to Platinum for Anticancer Drug Development

Poster Number

23C

Lead Author Major

Biological Sciences

Lead Author Status

Sophomore

Second Author Major

Biological Sciences

Second Author Status

Senior

Third Author Major

Pre-Pharmacy

Third Author Status

Sophomore

Fourth Author Major

Pre-Dental/Biology

Fourth Author Status

Sophomore

Fifth Author Major

Pre-Dental/Biology

Fifth Author Status

Sophomore

Format

Poster Presentation

Faculty Mentor Name

Qinliang Zhao

Faculty Mentor Department

Chemistry Department

Graduate Student Mentor Name

Rabeya Bosri

Graduate Student Mentor Department

Chemistry Department

Abstract/Artist Statement

Cancer, an illness causing uncontrollable cell division, has devastating effects on the lives of many, leading to extensive research in this field. It has been proven that platinum-based drugs are able to treat cancer in some form, but studies show that they have harmful side effects to the body, including but not limited to the kidneys and nervous system. For this reason, the search for a more selective and less resistant bifunctional platinum-based anticancer drug continues. The inclusion of histone deacetylase inhibitors (HDACi) has been taken into consideration. Histone deacetylase (HDAC) are enzymes that acetylate residual histone lysine and are actually overexpressed in particular cancer cells. AddingHDACi as a ligand to platinum, specifically targeting the cancer cells instead of the normal tissue, may prove effective . A loosened chromatin structure, due to the action of HDACi and therefore more prone for the Pt centers to attack the DNA, could be a possible outcome to this incorporation. Investigating ways these HDACi are designed and constructed could allow for further discoveries in their ability to increase selectivity for cancer cells and therefore provide innovation for cancer treatments overall. HDACi L19 was designed by altering the cap domain, a domain for recognizing surface proteins of the enzyme, the linker itself along with its length, as well as the zinc-binding domain. Mechanism and synthetic procedures of L19 will be focused on, more specifically, the detailed synthesis, purification, and characterization of L19-1 (4-acetamidophenethyl acetate), L19-2 (4-acetamido-3-nitrophenethyl acetate), L19-3 [2-(4-amino-3-nitrophenyl)ethan-1-ol], and L19-4 [4-(2-bromoethyl)-2-nitroaniline] will be discussed.

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

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Apr 29th, 10:00 AM Apr 29th, 1:00 PM

Design, Synthesis, and Characterization of a HDACi to coordinate to Platinum for Anticancer Drug Development

Information Commons, William Knox Holt Memorial Library and Learning Center

Cancer, an illness causing uncontrollable cell division, has devastating effects on the lives of many, leading to extensive research in this field. It has been proven that platinum-based drugs are able to treat cancer in some form, but studies show that they have harmful side effects to the body, including but not limited to the kidneys and nervous system. For this reason, the search for a more selective and less resistant bifunctional platinum-based anticancer drug continues. The inclusion of histone deacetylase inhibitors (HDACi) has been taken into consideration. Histone deacetylase (HDAC) are enzymes that acetylate residual histone lysine and are actually overexpressed in particular cancer cells. AddingHDACi as a ligand to platinum, specifically targeting the cancer cells instead of the normal tissue, may prove effective . A loosened chromatin structure, due to the action of HDACi and therefore more prone for the Pt centers to attack the DNA, could be a possible outcome to this incorporation. Investigating ways these HDACi are designed and constructed could allow for further discoveries in their ability to increase selectivity for cancer cells and therefore provide innovation for cancer treatments overall. HDACi L19 was designed by altering the cap domain, a domain for recognizing surface proteins of the enzyme, the linker itself along with its length, as well as the zinc-binding domain. Mechanism and synthetic procedures of L19 will be focused on, more specifically, the detailed synthesis, purification, and characterization of L19-1 (4-acetamidophenethyl acetate), L19-2 (4-acetamido-3-nitrophenethyl acetate), L19-3 [2-(4-amino-3-nitrophenyl)ethan-1-ol], and L19-4 [4-(2-bromoethyl)-2-nitroaniline] will be discussed.