Formula: C3H3BrN2SIn 2014 ,《Structure-Function Relationship of Thiazolide-Induced Apoptosis in Colorectal Tumor Cells》 was published in ACS Chemical Biology. The article was written by Brockmann, Anette; Strittmatter, Tobias; May, Sarah; Stemmer, Kerstin; Marx, Andreas; Brunner, Thomas. The article contains the following contents:
Thiazolides are a novel class of anti-infectious agents against intestinal intracellular and extracellular protozoan parasites, bacteria, and viruses. While the parent compound nitazoxanide (NTZ; 2-(acetolyloxy)-N-(5-nitro-2-thiazolyl)benzamide) has potent antimicrobial activity, the bromo-thiazolide RM4819 (N-(5-bromothiazol-2-yl)-2-hydroxy-3-methylbenzamide) shows only reduced activity. Interestingly, both mols. are able to induce cell death in colon carcinoma cell lines, indicating that the mol. target in intestinal pathogens and in colon cancer cells is different. The detoxification enzyme glutathione S-transferase of class Pi 1 (GSTP1) is frequently overexpressed in various tumors, including colon carcinomas, and limits the efficacy of antitumor chemotherapeutic drugs due to its detoxifying activities. In colorectal tumor cells RM4819 has been shown to interact with GSTP1, and GSTP1 enzymic activity is required for thiazolide-induced apoptosis. At present it is unclear which mol. structures of RM4819 are required to interact with GSTP1 and to induce cell death in colon carcinoma cell lines. Here, we demonstrate that novel thiazolide derivatives with variation in their substituents of the benzene ring do not significantly affect apoptosis induction in Caco-2 cells, whereas removal of the bromide atom on the thiazole ring leads to a strong reduction of cell death induction in colon cancer cells. We further show that active thiazolides require caspase activation and GSTP1 expression in order to induce apoptosis. We demonstrate that increased glutathione (GSH) levels sensitize colon cancer cells to thiazolides, indicating that both GSTP1 enzymic activity as well as GSH levels are critical factors in thiazolide-induced cell death. After reading the article, we found that the author used 5-Bromothiazol-2-amine(cas: 3034-22-8Formula: C3H3BrN2S)
5-Bromothiazol-2-amine(cas: 3034-22-8) belongs to anime. The reaction of alkyl halides, R―X, where X is a halogen, or analogous reagents with ammonia (or amines) is useful with certain compounds. Not all alkyl halides are effective reagents; the reaction is sluggish with secondary alkyl groups and fails with tertiary ones. Its usefulness is largely confined to primary alkyl halides (those having two hydrogen atoms on the reacting site).Formula: C3H3BrN2S
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica