Synthesis and Antimicrobial Activity Evaluation of Imidazole‐Fused Imidazothiadiazole Analogues

• Published in: ChemMedChem Vol. 16; no. 15; pp. 2354 - 2365
• Main Authors: Fang Yan Guo, Chang Ji Zheng, Wang, Meiyuan, Ai, Jiangping, Han, Lan Ying, Liu, Yang, Ye Fang Lu, Yang, Yu Xuan, Ming Guan Piao, Hu‐Ri Piao, Chun‐Mei Jin, Cheng, Hua Jin
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.08.2021
• Subjects: Aniline; Antifungal activity; Antifungal agents; Antimicrobial activity; Antimicrobial agents; Cytotoxicity; Fluconazole; Fungicides; Gatifloxacin; Gram-negative bacteria; Imidazole; Organic compounds; Selectivity; Thiadiazoles; Toxicity
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202100122

Three series of new imidazole‐fused imidazo[2,1‐b][1,3,4]thiadiazole analogues (compounds 20 a–g, 21 a–g, and 22 a–g) have been synthesized, and their antibacterial and antifungal activities have been evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans over Gram‐positive and ‐negative bacteria. N‐((4‐(2‐Cyclopropyl‐6‐(4‐fluorophenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)‐5‐(6‐methyl‐pyridin‐2‐yl)‐1H‐imidazol‐2‐yl)methyl)aniline (21 a) showed the highest activity against C. albicans (MIC50=0.16 μg/mL), 13 and three times that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21 a and 20 e did not show cytotoxicity against human foreskin fibroblast‐1 cells, and compound 21 a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents.