New imidazo[2,1-b][1,3,4]thiadiazole derivatives of thiazolidine-2,4-dione and rhodanine-3-acetic acid: Synthesis, characterization, evaluation of TGF-βRI inhibitory activity, cytotoxicity studies and mesoporous silica nanoparticle (MSN) delivery studies

• Main Author: Lagua, Faith Marie G.
• Format: text
• Published: Animo Repository 2019
• Subjects: Thiadiazoles—Derivatives—Synthesis; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/etd_doctoral/1448; https://animorepository.dlsu.edu.ph/cgi/viewcontent.cgi?article=2495&context=etd_doctoral
• Institution: De La Salle University

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.