1,3-dipolar cycloaddition reactions of the compound obtaining from cyclopentadiene-PTAD and biological activities of adducts formed selectively

Abstract

After known adduct (4) was synthesized by cycloaddition reaction of cyclopentadiene with 4-phenyl-1,2,4-triazoline-3,5-dione, seven new isoxazoline derivatives were synthesized from reactions of 4 with corresponding oximes prepared from benzaldehyde derivatives in the existence of the aqueous NaOCl in CH2Cl2 at 0 degrees C-RT via nitrile oxides. Four new pyrazoline derivatives were also synthesized from reactions of 4 with corresponding prepared reagents via nitrile imines. Selectively, each of all isoxazole and pyrazoline derivatives was synthesized by 1,3-dipolar cycloaddition reactions of compound 4 with the corresponding reagents. Based on the results of their biological activity analyses, K-i values for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glucosidase (alpha-Gly) enzymes were obtained in this range 32.15 +/- 5.73-107.44 +/- 19.52 22.57 +/- 4.30-186.07 +/- 23.51, and 69.08 +/- 8.54-528.07 +/- 38.46 nM, respectively. Besides that, these compounds were subjected to molecular docking to describe the interaction against AChE, BChE, and alpha-Gly enzymes in which important interactions were visualized and evaluated with residues of the binding region in each target enzyme.