Date of Publication

12-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Subject Categories

Chemistry

College

College of Science

Department/Unit

Chemistry

Thesis Adviser

Glenn V. Alea
Santiago Gomez-Ruiz

Defense Panel Chair

Jaime Raul O. Janairo

Defense Panel Member

Armando Victor M. Guidote, Jr.
Gerardo C. Janairo
Eric Camilo R. Punzalan
Roger S. Tan

Abstract/Summary

New imidazothiadiazole derivatives of thiazolidine-2,4-dione (8a-b) and rhodanine-3-acetic acid (7a-b) were synthesized and characterized. The synthesis involved the preparation of 5-(6-methylpyridin-2-yl)-1,3,4-thiadiazol-2-amine (4) followed by the condensation with different alpha-haloketones to yield the imidazo[2,1-b][1,3,4]thiadiazole precursors (5a-d). These precursors underwent a Vilsmeier-Haack reaction to generate the corresponding imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde derivatives. This was followed by Knoevenagel condensation to generate the target compounds in moderate to high yields. Compounds 7a-b and 8a-b were subjected to an ADP-GloTM (Promega) enzyme kinase assay with a TGF-βRI kinase and a p-38 α kinase to evaluate its TGF-βRI inhibitory activity and selectivity towards these enzymes. These compounds as well as their imidazothiadiazole precursors (5a-d) were also subjected to cytotoxicity studies on SW-480, SW-620, HT-29, DLD-1 and HaCaT cancer lines. A mesoporous silica nanodrug delivery system was made to incorporate each of the precursor imidazothiadiazole compounds (5a-d) and imidazo[2,1-b][1,3,4]thiadiazole derivatives (7a-b and 8a-b) to study the effect of the drug delivery system towards the improvement of the cytotoxicity of these compounds towards the cancer lines that were used in the MTT assay.

Abstract Format

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Accession Number

CDTG007969

Keywords

Thiadiazoles—Derivatives—Synthesis

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Embargo Period

1-10-2023

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