The synthesis and evaluation of anti-acetylcholinesterase activity of some 4(3H)-quinazolinone derivatives bearing substituted 1,3,4- thiadiazole

Uraz, Mine; Karakuş, Sevgi; Mohsen, Usama Abu; Kaplancıklı, Zafer Asım; Rollas, Sevim

doi:10.12991/marupj.259886

Cited by 11 publications

(3 citation statements)

References 22 publications

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“…Previously, 2-methyl-3-( o -tolyl)-4(3 H )-quinazolone (methaqualone) was used for sedation and sleep induction. Derivatives bearing a substituted 1,3,4-thiadiazole may show inhibitory activity on AChE enzyme . However, screening of compounds 4a–i for inhibition of electric eel (Electrophorus electricus) AChE only displayed the median inhibitory activities (IC 50 ) ranging from 57 to 266 μg/mL.…”

Section: Resultsmentioning

confidence: 99%

“…Derivatives bearing a substituted 1,3,4-thiadiazole may show inhibitory activity on AChE enzyme. 40 However, screening of compounds 4a–i for inhibition of electric eel ( Electrophorus electricus ) AChE only displayed the median inhibitory activities (IC 50 ) ranging from 57 to 266 μg/mL. It may be that Aedes aegypti AChE will show better inhibition, but this enzyme was unavailable.…”

Section: Resultsmentioning

confidence: 99%

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Potential for Aedes aegypti Larval Control and Environmental Friendliness of the Compounds Containing 2-Methyl-3,4-dihydroquinazolin-4-one Heterocycle

Nguyen

Ngo

et al. 2023

ACS Omega

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2-Methylquinazolin-4(3H)-one was prepared by the reaction of anthranilic acid, acetic anhydride, and ammonium acetate. The reaction of 2-methylquinazolin-4(3H)-one with N-aryl-2-chloroacetamides in acetone in the presence of potassium carbonate gave nine N-aryl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide compounds. The structures of these compounds were elucidated on the basis of their IR, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectrometry (HR-MS) spectral data. These synthesized compounds containing the 2-methyl-3,4-dihydroquinazolin-4-one moiety exhibited activity against Aedes aegypti mosquito larvae with LC 50 values of 2.085−4.201 μg/mL after 72 h exposure, which is also confirmed using a quantitative structure−activity relationship (QSAR) model. Interestingly, these compounds did not exhibit toxicity to the nontarget organism Diplonychus rusticus. In silico molecular docking revealed acetylcholine binding protein (AChBP) and acetylcholinesterase (AChE) to be potential molecular targets. These data indicated the larvicidal potential and environmental friendliness of these Naryl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide derivatives.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Potential for Aedes aegypti Larval Control and Environmental Friendliness of the Compounds Containing 2-Methyl-3,4-dihydroquinazolin-4-one Heterocycle

Nguyen

Ngo

et al. 2023

ACS Omega

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“…The quinazoline scaffold, as a privileged structure, has been used for the design and development of various therapeutic agents, including anticancer, antimicrobial, and anti-neurodegenerative agents 25 – 27 . Recently, several quinazoline-based compounds have been reported as effective agents for the treatment of Alzheimer’s disease 28 – 30 . Among these, a number of 2,4-disubstituted quinazoline derivatives have shown effects such as cholinesterase and Aβ aggregation inhibition 31 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, biological evaluation, molecular docking, and MD simulation of novel 2,4-disubstituted quinazoline derivatives as selective butyrylcholinesterase inhibitors and antioxidant agents

Sadeghian,

Razmi,

Khabnadideh

et al. 2024

Sci Rep

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Alzheimer’s disease is the most prevalent neurodegenerative disorder characterized by significant memory loss and cognitive impairments. Studies have shown that the expression level and activity of the butyrylcholinesterase enzyme increases significantly in the late stages of Alzheimer’s disease, so butyrylcholinesterase can be considered as a promising therapeutic target for potential Alzheimer’s treatments. In the present study, a novel series of 2,4-disubstituted quinazoline derivatives (6a–j) were synthesized and evaluated for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinestrase (BuChE) enzymes, as well as for their antioxidant activities. The biological evaluation revealed that compounds 6f, 6h, and 6j showed potent inhibitory activities against eqBuChE, with IC50 values of 0.52, 6.74, and 3.65 µM, respectively. These potent compounds showed high selectivity for eqBuChE over eelAChE. The kinetic study demonstrated a mixed-type inhibition pattern for both enzymes, which revealed that the potent compounds might be able to bind to both the catalytic active site and peripheral anionic site of eelAChE and eqBuChE. In addition, molecular docking studies and molecular dynamic simulations indicated that potent compounds have favorable interactions with the active sites of BuChE. The antioxidant screening showed that compounds 6b, 6c, and 6j displayed superior scavenging capabilities compared to the other compounds. The obtained results suggest that compounds 6f, 6h, and 6j are promising lead compounds for the further development of new potent and selective BuChE inhibitors.

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Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1 H )-one derivatives as inhibitors of cholinesterases

Sarfraz

Sultana

Rashid

et al. 2017

Bioorganic Chemistry

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In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC=1.6±0.10μM (AChE) and 3.7±0.18μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme.

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The synthesis and evaluation of anti-acetylcholinesterase activity of some 4(3H)-quinazolinone derivatives bearing substituted 1,3,4- thiadiazole

Cited by 11 publications

References 22 publications

Potential for Aedes aegypti Larval Control and Environmental Friendliness of the Compounds Containing 2-Methyl-3,4-dihydroquinazolin-4-one Heterocycle

Potential for Aedes aegypti Larval Control and Environmental Friendliness of the Compounds Containing 2-Methyl-3,4-dihydroquinazolin-4-one Heterocycle

Synthesis, biological evaluation, molecular docking, and MD simulation of novel 2,4-disubstituted quinazoline derivatives as selective butyrylcholinesterase inhibitors and antioxidant agents

Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1 H )-one derivatives as inhibitors of cholinesterases

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