Green synthesis and pharmacological screening of polyhydroquinoline derivatives bearing a fluorinated 5-aryloxypyrazole nucleus†
Abstract
A novel series of polyhydroquinoline scaffolds 8a–p has been designed and synthesized under ultrasonic irradiation by a one-pot three-component cyclocondensation reaction of 3-methyl-5-substituted aryloxy-1-phenyl-1H-pyrazole-4-carbaldehydes 3a–d with malononitrile 7 and various enhydrazinoketones 6a–e in the presence of piperidine as basic catalyst. All the synthesized compounds have been characterized by various spectroscopic techniques and elemental analysis. All the synthesized compounds were evaluated for their in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and also for their in vitro antimalarial activity against Plasmodium falciparum. Compounds 8c, 8i, 8j, 8l and 8m exhibited excellent antimalarial potency. The cytotoxicity of the synthesized compounds was tested using a bioassay of S. pombe cells at the cellular level. Compounds 8i, 8j, 8k and 8l were found to have maximum toxicity, while compounds 8e, 8m, 8c were found to be less cytotoxic. Some of them displayed luminous antibacterial activity and reasonable antituberculosis activity as compared with the first line drugs.