Fluorinated pyrrole incorporated 2-thiazolyl hydrazone motifs: a new class of antimicrobial and anti tuberculosis agents

In aim of obtaining novel bio-active compounds, a new series of fluorinated 1-(4-(aryl)thiazol-2-yl)-2-((1-(aryl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)hydrazines (5a–t) and 1-(4-(4-aryl)thiazol-2-yl)-2-((3-(2,4-dichlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazines (8a–d) were synthesized and screened for their antibacterial and antifungal activities. The potent compounds were further screened in vitro for anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Compounds 5a, 5c–5h and 5m were found to be good inhibitors of B. subtilis with MIC ranging from 0.2 to 0.8 µg mL⁻¹, which are nearly three to ten times more potent than the standard drug Ciprofloxacin. Compounds 5a, 5h–5k and 5o exhibited potent antifungal activity against C. albicans strain with MIC ranging from 0.4 to 1.6 µg mL⁻¹. Compounds 8a–8c were found to be excellent inhibitors of A. niger. Compounds 5a and 5k showed significant anti tubercular activity with MIC 3.12 and 6.25 µg mL⁻¹ respectively. Furthermore, highly active compounds were tested for their preliminary toxicity profile by hemolytic assay and were found to be non hemolytic at higher concentration with good selectivity index. Cytotoxicity of the potent compounds 5a, 5d, 5g, 5i and 5k was checked by MTT assay using normal embryonic kidney cell line HEK 293 and found to be non-toxic up to 50–200 times the MIC for antibacterial activity.