Design, synthesis and molecular modeling of pyrazole–quinoline–pyridine hybrids as a new class of antimicrobial and anticancer agents

•A series of 4H-quinoline derivatives have been synthesized.•Synthesized derivatives have been screened for in vitro anticancer.•Synthesized derivatives have been screened for in vitro antibacterial.•Enzyme inhibitory activity against EGFR and FabH.

A new series of pyrazole–quinoline–pyridine hybrids were designed based on molecular hybridization technique and synthesized by a base-catalyzed cyclocondensation reaction through one-pot multicomponent reaction. All compounds were tested for in vitro antibacterial and anticancer activities. Enzyme inhibitory activities of all compounds were carried out against FabH and EGFR. Of the compounds studied, majority of the compounds showed effective antibacterial as well as anticancer activity against used strains and cancer cell lines respectively. Compound 7k (IC50 = 0.51 ± 0.05 μM) against EGFR and 7b displayed the most potent inhibitory activity with IC50 of 3.1 μM against FabH as compared to other member of the series. In the molecular modeling study, compound 7k was bound in to the active pocket of EGFR with three hydrogen bond and one π–cation interaction with minimum binding energy ΔGb = −54.6913 kcal/mol, as well as compound 7b was bound in to the active site of FabH with hydrogen bond and π–sigma interactions with minimum binding energy ΔGb = −45.9125 kcal/mol.

Graphical abstractA new series of pyrazole–quinoline–pyridine hybrids were designed based on molecular hybridization technique and synthesized by a base-catalyzed cyclocondensation reaction through one-pot multicomponent reaction. All compounds were tested for in vitro antibacterial and anticancer activities. Enzyme inhibitory activities of all compounds were carried out against FabH and EGFR. Of the compounds studied, majority of the compounds showed effective antibacterial as well as anticancer activity against used strains and cancer cell lines respectively. Compound 7k (IC50 = 0.51 ± 0.05 μM) against EGFR and 7b displayed the most potent inhibitory activity with IC50 of 3.1 μM against FabH as compared to other member of the series.Figure optionsDownload full-size imageDownload as PowerPoint slide