Synthesis, molecular docking and some metabolic enzyme inhibition properties of biphenyl-substituted chalcone derivatives

The new synthesized biphenyl-substituted chalcone derivatives were evaluated against the human carbonic anhydrase isoenzymes I and II (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. The synthesized biphenyl-substituted chalcone derivatives showed Ki values in range of 14.71–62.95 nM against hCA I, 31.69–47.20 nM against hCA II, 4.33–16.97 nM against AChE, and 3.72–6.74 nM against BChE enzymes. The synthesized biphenyl-substituted chalcone derivatives exhibited effective inhibition profiles against indicated metabolic enzymes when compared to acetazolamide (for hCA I and II) and tacrine (for AChE and BChE). Molecular docking, MD simulation, and MM/PB(GB)SA calculations were applied for nine compounds. The best dock scores were obtained from compounds 21, 22 and 24, and the lowest △GMM/PBSA energy were determined as 19, 21 and 22. All results may contribute to the development of new drugs particularly to treat some disorders, which widespread display in the world including glaucoma and Alzheimer's diseases. © 2022 Elsevier B.V.