Enzyme Inhibition Properties and Molecular Docking Studies of 4‐Sulfonate Containing Aryl α‐Hydroxyphosphonates Based Hybrid Molecules

Abstract

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.

A Review on Recent Approaches on Molecular Docking Studies of Novel Compounds Targeting Acetylcholinesterase in Alzheimer Disease

“…Due to their biological activity and value as synthetic precursors for the synthesis of related organophosphonates such as aminophosphonates, alkoxy- and acyloxy-phosphonates, keto-phosphonates, and halophosphonates, hydroxyphosphonates have gained a lot of attention [ 85 , 86 ]. In addition, bis-hydroxyphosphonates make good diol monomers for the creation of phosphorus-containing polymers with flame-retardant qualities [ 87 ]. In their study Şahin, I. and co-workers [ 71 ], synthesized and developed molecular docking studies about sulfonate compounds with aryl α-Hydroxyphsphonate group.…”

“…PAS is a protein that is found at the entrance to the active site and is in charge of several crucial functions, including the interaction with β-amyloid. In the acyl binding pocket of AChE, it restricts the freedom of the substrates bound to the phenyl rings of Phe295 and Phe297 and promotes the catalysis of the substrate with the shortest acyl group, such as acetylcholine [ 87 ].…”

Synthesis of Novel Bromophenol with Diaryl Methanes—Determination of Their Inhibition Effects on Carbonic Anhydrase and Acetylcholinesterase

“…In order to investigate the in vitro inhibitory mechanisms of bromophenols ( 13 – 21 ), kinetic studies were performed at different concentrations of bromophenols and various substrates [ 85 , 86 ]. From the Lineweaver–Burk graphs, the IC 50 and K i values of bromophenol ( 13 – 21 ) derivatives were calculated, and the inhibition type of bromophenols ( 13 – 21 ) against AChE and hCAs was determined, as given in prior studies [ 87 , 88 , 89 ].…”

Phthalimide‐tethered imidazolium salts: Synthesis, characterization, enzyme inhibitory properties, and in silico studies

“…[43,44] Although there are other causes of AD, the following are the most common ones: agglomeration of amyloid-β peptides, cardiovascular diseases, low levels of acetylcholine (ACh), genetic, advanced age, people's lifestyle, diabetes, oxidative stress, hypertension, and vitamin B5 deficiency. [45][46][47] Research for AD disorder has focused on AChE inhibitors. AChE catalyzes the hydrolysis of AChI and drops the ACh level in the brain but inhibiting AChE increase neurotransmission.…”