The synthesis and characterization of select 2,4,5-triphenyl imidazoles and imidazo [1,5-a] pyridine compounds and the investigation of anti-proliferative properties in prostate cancer, 2021

Collection:
Atlanta University and Clark Atlanta University Theses and Dissertations
Title:
The synthesis and characterization of select 2,4,5-triphenyl imidazoles and imidazo [1,5-a] pyridine compounds and the investigation of anti-proliferative properties in prostate cancer, 2021
Creator:
Jackson, Janise J.
Date of Original:
2021-05
Subject:
Degrees, Academic
Dissertations, Academic
Location:
United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
Medium:
born digital
Type:
Text
Format:
application/pdf
Description:
The synthesis of select novel imidazole and imidazopyridine compounds were examined for anti-cancer properties. Heterocyclic ring systems have garnered vast attention due to their frequent occurrence in bioactive compounds. Nitrogen containing heterocycles are the most abundant form of small molecules with biological relevance. The work detailed here involves the synthesis of novel imidazopyridines, which includes both 2,4,5-triphenylimidazoles (tpIZ) and imidazo[1,5-a] pyridines (IMP) with the use of microwave assisted organic synthesis (MAOS) which afforded pure compounds within expedited reaction times. tpIZ compounds were synthesized via modification of salicylaldehyde derivatives via Williamson esterification followed by a one-pot synthesis using the functionalized salicylaldehydes, benzil and ammonium acetate in the presence of acetic acid, using open vessel microwave conditions. Development of a novel imidazo[1,5-a] pyridine compound, followed procedures like those used for tpIZ, using modified salicylaldehyde’s, di(2-pyridyl) ketone and ammonium acetate in acetic acid. Compounds were characterized using nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FT-IR). Use of MAOS eliminated unwanted biproducts and hydrolysis of desired compounds. Pure compounds were investigated to determine bioavailability as well as anti-proliferative properties in prostate cancer cells. Biochemical assay was employed to investigate the cytotoxic properties of the compounds against several prostate cancer cell lines. The examination of antiproliferative properties of tpIZ showed limited cytotoxic activity in metastatic prostate cancer cell lines; PC-3, DU-145, and LNCaP. At high concentrations tpIZ’s were not very toxic in inhibiting cancer cell growth and show crystallization due to insolubility after 72 hours. tpIZ treatment of immortalized non-malignant prostate cell line RWPE-1 showed decreased cell growth, indicative of compounds toxicity in normal prostate cells. Novel IMP showed cytotoxicity against PC-3 cells at lower molar concentrations than LY294002, a well-characterized inhibitor of phosphoinnositide030kinases (PI3K). Toxicity of IMP in RWPE-1 cells were less compared to the unfunctionalized parent IMP. The novel IMP has emerged as an ideal candidate as an anti-proliferative molecule in prostate cancer.
Date of award: 2021-05
Degree type: dissertation
Degree name: Doctor of Philosophy (PhD)
Granting institution: Clark Atlanta University
Department: Department of Chemistry
Advisor: Bu, Xiu-Ren
Metadata URL:
http://hdl.handle.net/20.500.12322/cau.td:2021_jackson_janise_j
Original Collection:
Atlanta University and Clark Atlanta University Theses and Dissertations
Holding Institution:
Atlanta University Center Robert W. Woodruff Library
Rights:
Rights Statement information

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