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The increasing resistance to antimicrobial drugs has instigated the crucial need for the discovery of novel compounds with different modes of action that could target both sensitive and resistant strains. For this purpose, we developed some new chalcone analogs. Herein, a novel series of hybrid biphenyl chalcones ( 17 - 24 ), which have organohalogens in their B ring, were synthesized and examined for their antimicrobial effect. The position of the substituent on ring B was changed to find the effect of the substitution on antimicrobial activity. Compounds  18 ,  19 , and  24  showed better antibacterial and antifungal activity when compared other compounds. Also, molecular docking studies on ATP binding site of  S. aureus  DNA gyrase for antibacterial targets were performed to elucidate the mechanism of antibacterial activity of synthesized compounds. Three of the most active compounds could be considered as lead compounds for the development of more new potent agents.

Synthesis, In Vitro Biological Evaluation, and Molecular Docking Studies of Novel Biphenyl Chalcone Derivatives as Antimicrobial Agents