New Diacetic Acids Containing Quinazolin‐4(3H)‐one: Synthesis, Characterization, Anticholinergic Properties, DFT Analysis and Molecular Docking Studies

Abstract

In this study, a new series of quinazolin-4(3H)-ones, which constitute an important part of biologically active heterocyclic compounds, were synthesized with excellent yields (99-94 %). The structures of the synthesized compounds (1-14) were characterized with Fourier-transform infrared (FTIR), nuclear magnetic resonance ( 1 H NMR -13 C NMR), and high-resolution mass spectroscopy (HRMS). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition properties were examined to evaluate the anticholinergic properties of the synthe-sized compounds. For AChE, molecules showed IC 50 in ranging of 16.27-9.12 μM and K i s in ranging of 19.20 � 0.68-4.83 � 0.19 μM. For BChE, molecules showed IC 50 in ranging of 16.77-8.50 μM and K i s in ranging of 10.35 � 2.15-3.38 � 0.25 μM. Molecular docking was performed to determine the predicted interactions between the synthesized molecules and enzymes. Additionally, Density-functional theory (DFT) studies were also carried out to clarify the electronic structures of compounds.

Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

“…For all compounds, peaks of the methyl carbons at position 2 of the quinazolinone ring were observed at δ 23.4–21.1 ppm. Chemical shifts, and number of the peaks are fully compatible with the structures and literature [20–22] …”

“…In another study investigating the anticholinergic properties of quinazolin‐4(3 H )‐ones, new diacetic acid derivatives containing quinazolin‐4(3 H )‐one nuclei were synthesized. The compounds synthesized in the study showed inhibition at the micromolar level and their activities were comparable to the standard compound tacrin [22] . As we mentioned above, all of the compounds synthesized within the scope of our study showed inhibition at the micromolar level and they are more effective than the standard inhibitor.…”

“…In this study, twenty compounds were synthesized. 3‐Amino‐2‐methylquinazolin‐4(3 H )‐one ( 3 ) was synthesized starting from methyl anthranilate in two steps according to the method given in our previous study [22] and it was used as amine reactant. Compound 3 was converted to target Schiff Base derivatives ( 3 a – s ) with good yields (88‐96 %) by using various sustituted benzaldehydes, heterocyclic aldehydes and allyl aldehydes (Figure 1).…”

“…Chemical shifts, and number of the peaks are fully compatible with the structures and literature. [20][21][22]…”

“…Chemical shifts, integrations and splits are fully compatible with the structures and literature. [20][21][22] In the 13 C NMR spectra of the compounds 3 a-s, peaks of the CH=N carbons of benzylidenamino moieties, C=O carbons of quinazolinone ring (C4) and C=N carbons of the quinazoline ring (C2) were seen at δ 171.4-158.6 ppm, δ 159.0-157.4 ppm and δ 154.6-153.2 ppm, respectively. Aromatic carbons appeared at δ 158.2-102.5 ppm.…”