Carboxylate‐ and Sulfonate‐Containing Quinazolin‐4(3H)‐one Rings: Synthesis, Characterization, and Carbonic Anhydrase I–II and Acetylcholinesterase Inhibition Properties

Abstract

Quinazolines are a group of bioactive heterocyclic compounds with a wide range of biological activities and have gained an important place in the design of active drugs with various targets due to their pharmacological properties. Carbonic anhydrase (CA) and acetylcholinesterase (AChE) inhibitors are very important pharmacologically. In this study, inhibition effects of newly synthesized quinazolin‐4(3H)‐one derivatives on human erythrocyte CA‐I (hCA‐I) and CA‐II (hCA‐II) isoenzyme and AChE activity were investigated. The structures of the novel compounds were characterized by fourier‐transform infrared (FTIR), nuclear magnetic resonance (NMR), and high‐resolution mass spectroscopy (HRMS). All molecules showed strong inhibitory effect in all three enzymes. 4‐[(4‐Oxo‐2‐(phenoxymethyl)quinazolin‐3(4H)‐ylimino)methyl]phenyl furan‐2‐carboxylate for hCA‐I (IC50: 205 nM), 4‐[(4‐oxo‐2‐(phenoxymethyl)quinazolin‐3(4H)‐ylimino)methyl]phenyl isobutyrate for hCA‐II (IC50: 209 nM), and 4‐[(4‐oxo‐2‐(phenoxymethyl)quinazolin‐3(4H)‐ylimino)methyl]phenyl propionate for AChE (IC50: 14.2 nM) were the molecules that showed the strongest inhibitory effect. Molecular docking studies were carried out to elucidate the possible interaction mechanism of the molecules in the active site of the enzymes. The affinity scores of the most active compounds for hCA‐I, hCA‐II, and AChE were determined as −134.765, −147.423, and −175.354 MolDock Score, respectively.

Synthesis, Characterization, Bioactivity Impacts of New Anthranilic Acid Hydrazones Containing Aryl Sulfonate Moiety as Fenamate Isosteres

“…Therefore, finding and creating both a preventive and a curative treatment for AD is the researchers' ultimate goal. [32] The inhibitory effects of the novel compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) on AChE are shown in Table 2. The AChE inhibition profiles of the compounds evaluated here were quite interesting.…”

“…CA inhibitors are the therapeutic agents used to control the hyper activity of CA. CAI have been prescribed and administered for the treatment of glaucoma, diuresis, epilepsy, osteoporosis, and gastric ulcer [9,10] . In the central and peripheral nervous systems of vertebrates and invertebrates, cholinesterases hydrolyze the neurotransmitter acetylcholine.…”

“…It may result in a number of health issues, including nerve damage, retinopathy, chronic renal disease, cardiovascular disease, and chronic kidney failure. Treatment for this fatal condition can benefit from the inhibition of these enzymes [3,4] . Carbonic anhydrase (CA) is present in red blood cells, renal tubules, and osteoclasts.…”

“…CAI have been prescribed and administered for the treatment of glaucoma, diuresis, epilepsy, osteoporosis, and gastric ulcer. [9,10] In the central and peripheral nervous systems of vertebrates and invertebrates, cholinesterases hydrolyze the neurotransmitter acetylcholine. The neurotransmitter ChE is in charge of carrying nerve impulses to the body's cholinergic synapses.…”

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

“…In a recent study by Tokalı et al ., inhibition properties of the new quinazolin‐4(3 H )‐one analogues against hCA I–II were evaluated in vitro and in silico . They reported that the new compounds showed inhibition at the nanomolar level and that compound 4‐[(4‐Oxo‐2‐(phenoxymethyl)quinazolin‐3(4 H )‐ylimino)methyl]phenyl furan‐2‐carboxylate (IC 50 : 205 nM) was the most potent compounds in the series for hCA I and compound 4‐[(4‐oxo‐2‐(phenoxymethyl)quinazolin‐3(4 H )‐ylimino)methyl]phenyl isobutyrate (IC 50 : 209) nM for hCA II [31] . When the results of this study are compared with our study, it is seen that our compounds have lower IC 50 values.…”