Synthesis of pyrrolo[3,2-c]carbazole-2-carbohydrazides and pyrrolo[3,2-c]carbazol-2-yl-1,3,4-oxadiazoles and their in vitro antibacterial evaluation

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.