Unique Carbazole-Oxadiazole Derivatives as New Potential Antibiotics for Combating Gram-Positive and -Negative Bacteria

• Published in: Journal of medicinal chemistry 2022-04, Vol.65 (8), p.6171-6190
• Main Authors: Xie, Yun-Peng, Sangaraiah, Nagarajan, Meng, Jiang-Ping, Zhou, Cheng-He
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacteria; Carbazoles - pharmacology; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Oxadiazoles - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.2c00001

Novel carbazole-oxadiazoles were developed as new potential antibacterial agents to combat dreadful resistance. Some target compounds displayed predominant inhibitory effects on the tested Gram-positive and -negative bacteria, and carbazole-oxadiazoles 5g, 5i–k, 16a–c, and tetrazole analogues 23b–c were found to be efficient in impeding the growth of MRSA and Pseudomonas aeruginosa ATCC 27853 (MICs = 0.25–4 μg/mL). Furthermore, compounds 5g and 23b–c not only possessed rapid bactericidal ability and low tendency to develop resistance but also exhibited low cytotoxic effects toward Hek 293T, HeLa, and red blood cells (RBCs), especially molecule 5g also showed low toxicity in vivo, which showed the therapeutic potential of these compounds. Further exploration indicated that compounds 5g, 5i, and 23b–c could disintegrate the integrity of bacterial cell membranes to leak the cytoplasmic contents, thus exerting excellent antibacterial effects. These facts mean that carbazole-based antibacterial agents might have bright prospects in confronting bacterial infections.