Natural products play an important role for the development of most of the biologically active compounds due to the presence of enormous structure and chemical diversity which cannot be matched by any synthetic libraries of small molecules.From all the approved antibacterial drugs approximately 68%of them are natural products or their derivatives.Berberine is a natural product with unique structure,a quaternary nitrogen and a large desirable π-conjugated backbone enables berberine-based derivatives to readily bind with biomolecules like deoxyribonucleic acid(DNA)or an enzyme via noncovalent forces such as π–π stacking and electronic interactions,thus exerting potent biological activities.Herein,we are interested to synthesize a series of hybrids of berberine and metronidazole as a novel class of antibacterial agents.