Synthesis, characterization of some novel 1,3,4-oxadiazole compounds containing 8-hydroxy quinolone moiety as potential antibacterial and anticancer agents

Abstract

In the present work a series of novel derivatives of 8-hydroxy quinolone substituted 1,3,4-oxadiazole compounds were synthesized by convergent synthetic method and studied for their antibacterial and anticancer properties. The cell lines used for cytotoxic evaluation were HeLa , Caco-2 and MCF7 . The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e . The ethyl ester was converted into corresponding carbohydrazide 3a-e . Carbohydrazides are reacted with chloroacetic acid, phosphorous oxytrichloride and irradiated with microwave in order to obtain the various key intermediates 2-(chloromethyl)-5-(substituted phenyl)-1,3,4-oxadiazole 4a-e . The 2-(chloromethyl)-5-(substituted phenyl)-1,3,4-oxadiazole was reacted with 8-hydroxy quinolone in presence of sodium hydride and obtained a series of 8-hydroxy quinoline substituted 1,3,4-oxadiazoles 5a-e . Among the synthesised compounds, the cytotoxicity of the compound 5b i.e. 8-{[5-(2,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl]methoxy}quinoline against MCF7 with IC 50 of 5.3µM and the compound 5e i.e. 8-{[5-(4-bromophenyl)-1,3,4-oxadiazol-2-yl]methoxy}quinoline showed MIC of < 6.25µg/mL against Staphylococcus aureus which is comparable with the known standards. The standards used for cytotoxic evaluation was 5-fluorouracil and for antibacterial was nitrofurazone