Synthesis, Characterization, Docking and Study of Inhibitory Action of Some Novel C‐Alkylated Chalcones on 5‐LOX Enzyme

Abstract

Abstract A series of C‐alkylated chalcones on ring ‘B’ of C 6 ‐C 3 ‐C 6 system of the basic flavonoid skeleton were synthesized by taking different alkyl substituted aldehydes by conventional approaches. The compounds ( 5 a‐l ) were obtained by condensing di‐ O ‐methylated phloroacetophenone with various alkylated (methyl, di‐methyl, ethyl and n‐propyl) substituted aromatic aldehydes ( 4 a‐l ) and characterized by different spectroscopic methods (IR, NMR, LC–MS and elemental analysis) and further studied their inhibitory action on 5‐lipoxygenase (5‐LOX) enzyme. The compounds (E)‐3‐(4‐ethoxy‐5‐methoxy‐2‐methylphenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl) prop‐2‐en‐1‐one ( 5 k ), (E)‐3‐(2,4‐dimethoxy‐5‐methylphenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxy phenyl)prop‐2‐en‐1‐one ( 5 i ), (E)‐3‐(4,5‐dimethoxy‐2‐methylphenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl)prop‐2‐en‐1‐one ( 5 j ), and (E)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl)‐3‐(2‐methoxy‐4,5‐dimethylphenyl)prop‐2‐en‐1‐one ( 5 l ) showed a significant 5‐LOX enzyme inhibitory action with IC 50 ranging between 49.1 and 52.3 μ M, whereas positive control curcumin exhibited IC 50 of 22 μ M. The molecular docking simulation study revealed that the compounds were well accommodated in the allosteric site of the enzyme, 5‐LOX.