Synthesis, characterization, in silico molecular docking study and biological evaluation of a 5-(phenylthio) pyrazole based polyhydroquinoline core moiety

A multicomponent cyclocondensation reaction has been developed by incorporating 3-methyl-5-substituted phenylthio-1-phenyl-1H-pyrazole-4-carbaldehydes 3a-c, various enaminones 6a-c and different active methylene compounds 7a-c (malononitrile 7a/ethylcaynoacetate 7b/caynoacetamide 7c) in the presence of piperidine as a basic catalyst, to afford a combinatorial library of polyhydroquinoline scaffolds, i.e. 8a-p. The targeted compounds were synthesized in good to excellent yields (71-84%). All the synthesized compounds have been characterized by H-1 NMR, C-13 NMR, IR, mass spectrometric techniques and elemental analysis. All the synthesized compounds were evaluated in vitro for their antibacterial, antitubercular and antimalarial activities. An in silico molecular docking study as well as in silico pharmacokinetics evaluation have been carried out. Many candidates of this new class revealed noticeable activities against first line drugs.