52057-90-6Relevant articles and documents
N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides bearing heteroaromatic rings as novel antibacterial agents: Design, synthesis, biological evaluation and target identification
Xue, Wenjie,Li, Xueyao,Ma, Guixing,Zhang, Hongmin,Chen, Ya,Kirchmair, Johannes,Xia, Jie,Wu, Song
, (2020/02/04)
Due to the occurrence of antibiotic resistance, bacterial infectious diseases have become a serious threat to public health. To overcome antibiotic resistance, novel antibiotics are urgently needed. N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides are a potential new class of antibacterial agents, as one of its derivatives was identified as an antibacterial agent against S. aureus. However, no potency-directed structural optimization has been performed. In this study, we designed and synthesized 37 derivatives, and evaluated their antibacterial activity against S. aureus ATCC29213, which led to the identification of ten potent antibacterial agents with minimum inhibitory concentration (MIC) values below 1 μg/mL. Next, we performed bacterial growth inhibition assays against a panel of drug-resistant clinical isolates, including methicillin-resistant S. aureus, and cytotoxicity assays with HepG2 and HUVEC cells. One of the tested compounds named 1-ethyl-4-hydroxy-2-oxo-N-(5-(thiazol-2-yl)-1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-3-carboxamide (g37) showed 2 to 128-times improvement compared with vancomycin in term of antibacterial potency against the tested strains (MICs: 0.25–1 μg/mL vs. 1–64 μg/mL) and an optimal selective toxicity (HepG2/MRSA, 110.6 to 221.2; HUVEC/MRSA, 77.6–155.2). Further, comprehensive evaluation indicated that g37 did not induce resistance development of MRSA over 20 passages, and it has been confirmed as a bactericidal, metabolically stable, orally active antibacterial agent. More importantly, we have identified the S. aureus DNA gyrase B as its potential target and proposed a potential binding mode by molecular docking. Taken together, the present work reports the most potent derivative of this chemical series (g37) and uncovers its potential target, which lays a solid foundation for further lead optimization facilitated by the structure-based drug design technique.
Preparation method and application of long carbon chain thiadiazole
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Paragraph 0033; 0034; 0035, (2017/02/23)
The present invention belongs to the field of organic corrosion inhibitor. A preparation method of long carbon chain thiadiazole is as follows: (1) grinding carboxylic acid, thiosemicarbazide and a solid super acidic catalyst in a ball mill; (2) adding the ground mixture into a reaction flask, at heating with 500W microwave power auxiliary irradiation for 5-10 min, extracting the reaction mixture by using an organic solvent, recovering the solid super acid, concentrating to obtain a solid, conducting base precipitation, filtration and purification on the to solid obtain 2-amino-5-alkyl-1,3,4-thiadiazole. The solid super acidic catalyst has excellent catalytic activity, can avoid environmental pollution caused by concentrated sulfuric acid catalysis, and can be reused; by grinding, the starting materials are completely encased in the solid super acid, and react completely under microwave conditions; and the method has the advantages of short reaction time, high yield and easiness to operation control. The thiadiazole compound has corrosion inhibition effect on copper in an acidic medium, and maintains the inhibition effect of more than 90% under strong acid conditions.
