Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression

Abed, Ali Adnan; Adnan Abid, Mohammed; Turki, Ahmed; Haroon, Muhammad; Mehmood, Hasnain; Akhtar, Tashfeen; Woodward, Simon

Abstract

Cyclization of substituted thiosemicarbazones with 3-bromo-1,1,1-trifluoroacetone affords new 2-(arylidenehydrazinyl)-4-trifluoromethylthiazoles (3 a–m, 13 examples, 71–89 %). These compounds were synthesized in two steps and characterized using 1H-, 13C-NMR, FTIR spectroscopy, and HRMS. All of these compounds show potent activity against both Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia) bacterial strains. The compounds 2-(2-(1-(4-fluorophenyl) ethylidene)hydrazinyl)-4 (trifluoromethyl)thiazole (3 b), 2-(2-(2-hydroxy-3-methylbenzylidene) hydrazinyl)-4-(trifluoromethyl)thiazole (3 c), and 2-(2-(3-fluorobenzylidene) hydrazinyl)-4-(trifluoromethyl) thiazole (3 k) show optimal minimum inhibitory concentration (MIC) values of 16 μg/mL against E. coli and (32, 32, and 8 μg/ml) against K. pneumonia, respectively. Using a qRT-PCR technique the gene expression of two different genes (FLU and mexB) was determined. Most of these compounds (3 a, d–j, l, m) exhibited downregulation of these genes for both types of bacteria, whereas the gene expressions were unaffected after treating 3 b, 3 c and 3 k. This means that although these compounds were able to inhibit bacterial growth, they did not target the FLU and mexB genes in both types of bacteria. These findings suggest further investigations for lead optimization could provide viable antibiotics due to their structural similarity with some commercially available antibiotics.

Citation

Abed, A. A., Adnan Abid, M., Turki, A., Haroon, M., Mehmood, H., Akhtar, T., & Woodward, S. (2024). Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression. ChemistrySelect, 9(17), Article e202401206. https://doi.org/10.1002/slct.202401206

• Journal Article Type: Article
• Acceptance Date: Apr 2, 2024
• Online Publication Date: Apr 26, 2024
• Publication Date: May 3, 2024
• Deposit Date: May 16, 2024
• Publicly Available Date: Apr 27, 2025
• Electronic ISSN: 2365-6549
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 17
• Article Number: e202401206
• DOI: https://doi.org/10.1002/slct.202401206
• Public URL: https://nottingham-repository.worktribe.com/output/34865449
• Publisher URL: https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/slct.202401206