Abstract

A number of novel pyrrolo[3,2-c]carbazole-2-carbohydrazides 5a–d was prepared from readily available 6-methyl-1,6-dihydropyrrolo[3,2-c]carbazole-2-carboxylate 3 and underwent cyclodehydration to produce the corresponding 2-(6-ethyl-1,6-dihydropyrrolo[3,2-c]carbazol-2-yl)-1,3,4-oxadiazoles 6a–d with p-toluenesulfonyl chloride (p-TsCl) and N,N-diisopropylethylamine (DIPEA) as dehydrative reagents. The structures of the targeted compounds were confirmed through ¹H NMR, ¹³C NMR, IR, mass spectrometry and single crystal X-ray diffraction techniques. Moreover, the antibacterial properties of the synthesized compounds were evaluated against colistin resistant (ColR) Klebsiella pneumoniae, ColR Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. Among the synthesized compounds, 5d was found to be active on ColR K. pneumoniae (MIC = 64 µg/mL) while compounds 4 (MIC= <64 µg/mL) and 6a (MIC==<64 µg/mL) were active on E. coli. Preliminary assay showed that the pyrrolo[3,2-c]carbazole-2-carbohydrazides and 2-(6-methyl-1,6-dihydropyrrolo[3,2-c]carbazol-2-yl)-1,3,4-oxadiazoles showed promising antibacterial activity on important nosocomial multi drug resistant (MDR) pathogens.

摘要

许多新型吡咯并[3,2-c]咔唑-2-碳酰肼5a-d由现成的6-甲基-1,6-二氢吡咯并[3,2-c]咔唑-2-羧酸酯3制备并进行环脱水用对甲苯磺酰氯 ( p- TsCl)制备相应的 2-(6-乙基-1,6-二氢吡咯并[3,2-c]咔唑-2-基)-1,3,4-恶二唑6a–d和N,N-二异丙基乙胺(DIPEA)作为脱水试剂。目标化合物的结构经¹ H NMR、¹³C NMR、IR、质谱和单晶X射线衍射技术。此外，还评估了合成化合物对耐粘菌素 (ColR)肺炎克雷伯菌、ColR鲍曼不动杆菌、铜绿假单胞菌、大肠杆菌和金黄色葡萄球菌的抗菌性能。在合成的化合物中，发现5d对肺炎克雷伯菌(MIC = 64 µg/mL)有活性，而化合物4 (MIC= <64 µg/mL) 和6a (MIC==<64 µg/mL) 有活性关于大肠杆菌. 初步分析表明吡咯并[3,2-c]咔唑-2-碳酰肼和2-(6-甲基-1,6-二氢吡咯并[3,2-c]咔唑-2-基)-1,3,4 -恶二唑对重要的医院内多重耐药 (MDR) 病原体显示出有希望的抗菌活性。