Synthesis, 3D pharmacophore, QSAR and docking studies of novel quinazoline derivatives with nitric oxide release moiety as preferential COX-2 inhibitors

Farag, Doaa Boshra; Farag, Nahla A.; Esmat, Ahmed; Abuelezz, Sally A.; Ibrahim, Eman; Ella, Dalal A. Abou El

doi:10.1039/c4md00392f

Cited by 23 publications

(13 citation statements)

References 43 publications

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“…The accessibility of 4(3H) derivatives and the versatility of their biological activities attract attention to this class of compounds. In the last three decades, many studies have been conducted on the anticancer, [12,13] antimicrobial and antifungal, [14] antiinflammatory, [15] antioxidant, [16] anticonvulsant, [17] antitumor, [18] antileishmanial, [19] antihistaminic, [20] antiviral, [21] anticholinergic [22,23] and antidiabetic [24,25] properties of quinazolinones.…”

Section: Introductionmentioning

confidence: 99%

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

Tokalı¹,

Kaya²,

Öztekіn³

et al. 2023

ChemistrySelect

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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.

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Section: Introductionmentioning

confidence: 99%

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

Tokalı¹,

Kaya²,

Öztekіn³

et al. 2023

ChemistrySelect

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“…The 3D‐QSAR Pharmacophore Generation protocol (HypoGen protocol of CATALYST; 13) was applied using Discovery Studio 2.5 software to create 10 predictive pharmacophore models via aligning different conformations in which the molecules were likely to bind with the receptor pharmacophore models. [ 24 ]…”

Section: Resultsmentioning

confidence: 99%

Synthesis of new arylazopyrazoles as apoptosis inducers: Candidates to inhibit proliferation of MCF‐7 cells

Ismail

Soliman

Sabour

et al. 2020

Archiv der Pharmazie

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New 4‐arylazo‐3,5‐diamino‐1H‐pyrazole derivatives substituted in the 4‐aryl ring with the acetyl moiety were designed and synthesized. The antiproliferative activity of the novel arylazopyrazoles was examined against the MCF‐7 cell line. Among all target compounds, 8b (IC50 3.0 µM) and 8f (IC50 4.0 µM) displayed higher cytotoxicity as compared with the reference standard imatinib (IC50 7.0 µM). Further studies to explore the mechanism of action were performed on the most active hit of our library, 8b, via anti‐CDK2 kinase activity. It demonstrated good inhibitory effects for CDK2 (IC50 0.24 µM) with 62.5% inhibition, compared with imatinib. The cell cycle analysis in the MCF‐7 cell line revealed apoptosis induction by 8b and cell cycle arrest at the S phase. Docking in the CDK2 active site and pharmacophore modeling confirmed the affinity of 8b to the CDK2 active site. Absorption, distribution, metabolism, and excretion studies revealed that our target compounds are orally bioavailable, with no permeation through the blood–brain barrier.

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“…A mixture of 2‐aminobenzoic acid (1 mmol) and acetic anhydride (2 mmol) was refluxed at 140 °C for 3 h. Completion of the reaction and formation of oxazine 3 was monitored by thin layer chromatography (TLC). The reported method for the preparation of 4 [29] involves the isolation of the latter, followed by refluxing with hydrazine hydrate (2 mmol) for 2–3 h. Oxazine 3 was generated in situ , excess acetic anhydride evaporated and then reacted with hydrazine hydrate at 5 °C (exothermic reaction), using hexane as a solvent. The purpose of hexane was to facilitate the precipitation of compound after complete addition of hydrazine hydrate.…”

Section: Methodsmentioning

confidence: 99%

Cytotoxicity and Antibacterial Evaluation of O‐Alkylated/Acylated Quinazolin‐4‐one Schiff Bases

Manhas

Singh

Mocktar

et al. 2021

Chemistry & Biodiversity

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A series of quinazolin‐4‐one Schiff bases were synthesized and tested in vitro for their cytotoxicity against two cancerous cell lines (MCF‐7, Caco‐2) and a human embryonic cell line (HEK‐293) including their antibacterial evaluation against two Gram‐positive and four Gram‐negative bacterial strains. Most of the quinazoline‐Schiff bases exhibited potent cytotoxicity against Caco‐2. 3‐[(Z)‐({4‐[(But‐2‐yn‐1‐yl)oxy]phenyl}methylidene)amino]‐2‐methylquinazolin‐4(3H)‐one (6f) with the O‐butyne functional group displayed three‐fold higher cytotoxic activity (IC50=376.8 μM) as compared to 5‐fluorouracil (5‐FU; IC50=1086.1 μM). However, all compounds were found to be toxic to HEK‐293, except for 3‐[(Z)‐({4‐[(2,4‐difluorophenyl)methoxy]phenyl}methylidene)amino]‐2‐methylquinazolin‐4(3H)‐one (6h) that showed ∼three‐fold lower toxicity and higher selectivity index than 5‐FU. Structure–activity relationship (SAR) analysis revealed that O‐alkylation generally increased the anticancer activity and selectivity of quinazoline‐4‐one Schiff bases toward Caco‐2 cells. The fluorinated Schiff‐base generally exhibited even more significant cytotoxic activity compared to their chlorine analogs. Surprisingly, none of the quinazoline‐4‐one Schiff bases displayed encouraging antibacterial activity against the bacterial strains investigated. Most of the compounds were predicted to show compliance with the Lipinski parameters and ADMET profiles, indicating their drug‐like properties.

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Synthesis, 3D pharmacophore, QSAR and docking studies of novel quinazoline derivatives with nitric oxide release moiety as preferential COX-2 inhibitors

Abstract: Four novel series of quinazoline derivatives IIIa–c, VIa–c and their NO-hybrid molecules as nitrate esters Va–c and VIIIa–c have been synthesized and evaluated for their anti-inflammatory activity in vivo and in vitro.

Cited by 23 publications

References 43 publications

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

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

Synthesis of new arylazopyrazoles as apoptosis inducers: Candidates to inhibit proliferation of MCF‐7 cells

Cytotoxicity and Antibacterial Evaluation of O‐Alkylated/Acylated Quinazolin‐4‐one Schiff Bases

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