Novel benzo[b]xanthene derivatives: Bismuth(III) triflate‐catalyzed one‐pot synthesis, characterization, and acetylcholinesterase, glutathione S‐transferase, and butyrylcholinesterase inhibitory properties

Abstract

In this study, 3,4‐dihydro‐12‐aryl‐1H‐benzo[b]xanthene‐1,6,11‐(2H,12H)trione compounds were obtained through one‐pot condensation of various substituted aromatic aldehydes, 2‐hydroxy‐1,4‐naphthoquinone, and dimedone in the presence of Bi(OTf)3 as a green and reusable catalyst. The structural characterization of these novel substituted benzo[b]xanthenes was performed by spectroscopic methods, and their inhibitory actions against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and glutathione S‐transferase (GST) were investigated. GST is an enzyme responsible for removing toxic molecules during Phase II reactions in the detoxification mechanism. The AChE and BChE enzymes, which are called cholinesterases, are among the enzymes that occur especially during dementia such as brain damage or Alzheimer's disease. Inhibition effects of the benzo[b]xanthene derivatives on AChE, BChE, and GST were found at the millimolar level. The best inhibitor for GST is compound 4a (31.18 ± 6.13 mM), for AChE, it is compound 4d (28.16 ± 3.46 mM), and for BChE, it is compound 4f (36.24 ± 3.19 mM). Compound 4a inhibited the dimerization of GST subunits, and compounds 4d and 4f directly inhibited the catalytic activity by interacting with the catalytic active site or a related site of the AChE and BChE enzymes, respectively.

Design, synthesis, molecular docking, and some metabolic enzyme inhibition properties of novel quinazolinone derivatives

“…All compounds were prepared with the Ligprep module [70] according to the method described in previous studies. [71] Then, the pharmacokinetic properties of the compounds were calculated using the Qikprop module. [72] The structures were made ready for docking studies using the Protein Preparation Wizard module.…”

“…Binding site prediction and evaluation of the sites were performed according to the method described in previous studies. [71] The induced-fit docking method [76] was tested with the redocking process before the compounds were docked and after molecular docking studies of the most effective compounds were performed using the induced-fit docking module. [71] CONFLICTS OF INTEREST…”

Design and Synthesis of Novel Dual Cholinesterase Inhibitors: In Vitro Inhibition Studies Supported with Molecular Docking

“…The results of the molecular docking study are similar to those suggesting that the most effective derivative, 2f, of benzimidazolium salts showed π-π stacking interactions between benzene ring moiety and the residues of Tyr 337 and Tyr341. [46] Turhan et al [47] investigated the effects of benzo[b]xanthene compounds and found similar hydrophobic and π-π stacking interactions.…”

Volume 5 Issue 1

“…Bacteria have been found to produce IAA that may induce root growth directly by stimulating plant cell elongation and cell division or indirectly by ACC deaminase activity 8,10 . Microbes that produce IAA can only promote host plant growth to a certain extent, an excess of which can have negative effects, a trait commonly found in pathogenic microbes 5 .…”

“…Some of the strains of rhizobacteria e.g. Acetobacter diazotrophicus, Rhizobium phaseoli, Herbaspirillum seropedicae, Bacillus cereus, B. macroides, B. licheniformis, and B. pumilus, Burkholderia cepacia SE4, A. chroococcum SE370, and have been known to produce IAA which support plant growth promotion 5,[8][9][10][11] .…”