In this study, a series of new hybrid molecules containing two important functional groups on the same skeleton were designed. 4-Hydroxybenzaldehyde and its two different derivatives were converted into their respective sulphonates by interacting with tosylchloride and methanesulfonyl chloride. Then, the desired molecules were synthesized by adding diethoxyphosphonate to the aldehyde group. Also, novel synthesis of hybrid compounds (4a-c and 5a-c) were tested toward some metabolic enzymes like carbonic anhydrase I and II isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE) enzyme. The synthesis of hybrid compounds (4a-c and 5a-c) showed Ki values of in range of 25.084±4.73-69.853±15.19 nM against hCA I, 32.325±1.67-82.761±22.73 nM against hCA II and 1.699±0.25 and 3.500±0.91 nM against AChE. For these compounds, compound 4c showed maximum inhibition effect against hCA I and hCA II isoenzymes and compound 5b showed maximum inhibition effect against AChE enzyme. By performing docking studies of the most active compounds for their binding modes and interactions were determined.
Keywords: acetylcholinesterase; carbonic anhydrase; enzyme inhibition; molecular docking studies; α-hydroxy phosphonates.
© 2022 Wiley-VHCA AG, Zurich, Switzerland.