Synthesis of novel 2-phenyl-3-[2-(substituted amino) ethylamino] quinazolin-4(3H)-ones as a new class of H1-antihistaminic agents

Alagarsamy, V.; Sundar, P. Shyam; Gobinath, M.; Nivedhitha, S.; Parthiban, P.; Shankar, D.; Sulthana, M. T.; Solomon, V. Raja

doi:10.1007/s00044-012-0243-3

Cited by 4 publications

(5 citation statements)

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“…antihistaminic, [28] anti-inflammatory, [29] antileishmanial, [30] antioxidant and DNA protective, [31] antiviral, [32] anticholinergic [33] antidiabetic [34] and inhibitor of carbonic anhydrase [35,36] and acetylcholinesterase [23] properties of quinazolinone derivatives.…”

Section: Chemistryselectmentioning

confidence: 99%

“…The accessibility of 4(3 H ) derivatives and the versatility of their biological activities attract attention to this class of compounds. There are many studies in the literature showing anticancer [24,25] antimicrobial, [26] anticonvulsant, [27] antihistaminic, [28] anti‐inflammatory, [29] antileishmanial, [30] antioxidant and DNA protective, [31] antiviral, [32] anticholinergic [33] antidiabetic [34] and inhibitor of carbonic anhydrase [35,36] and acetylcholinesterase [23] properties of quinazolinone derivatives.…”

Section: Introductionmentioning

confidence: 99%

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

2023

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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.

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Section: Chemistryselectmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2023

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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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“…These compounds have demonstrated their potential such as anticancer (Zhu et al., 2014), anti‐inflammatory (Rathore et al., 2017) anti‐viral (Selvakumar et al., 2017), anti‐oxidant (Gürsoy Kol et al., 2016), anti‐microbial (Salem et al., 2021), analgesic (Ahmadi et al., 2011), and anti‐leishmanial (Süleymanoğlu et al., 2018). On the other hand, quinazolines and/or quinazolinone derivatives are also privileged compound class with a broad spectrum of biological activities such as anti‐cancer (Tokalı, Şenol, et al., 2023) anti‐microbial and anti‐fungal (Mostafavi et al., 2019), anti‐convulsant (Patel et al., 2016), anti‐histaminic (Alagarsamy et al., 2013), anti‐inflammatory (Farag et al., 2015), anti‐leishmanial (Romero et al., 2019), anti‐oxidant and DNA protective (Kuntikana et al., 2016), anti‐tumor (Rahmannejadi et al., 2020), anti‐viral (Wang et al., 2020), anti‐cholinergic (Tokalı et al., 2021), and anti‐diabetic (Tokalı, Demir, et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

A series of quinazolin‐4(3H)‐one‐morpholine hybrids as anti‐lung‐cancer agents: Synthesis, molecular docking, molecular dynamics, ADME prediction and biological activity studies

Tokalı,

Şenol,

Ateşoğlu

et al. 2024

Chem Biol Drug Des

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In this study, we synthesized 15 novel quinazoline‐morpholinobenzylideneamino hybrid compounds from methyl anthranilate and we assessed their cytotoxicity via in vitro assays against A549 and BEAS‐2B cell lines. Molecular docking studies were conducted to evaluate the protein‐ligand interactions and inhibition mechanisms on nine different molecular targets, while molecular dynamics (MD) simulations were carried out to assess the stability of the best docked ligand–protein complexes. Additionally, ADME prediction was carried out to determine physicochemical parameters and drug likeness. According to the cytotoxicity assays, compound 1 (IC50 = 2.83 μM) was found to be the most active inhibitor against A549 cells. While the selectivity index (SI) of compound 1 is 29, the SI of the reference drugs paclitaxel and sorafenib, used in this study, are 2.40 and 4.92, respectively. Among the hybrid compounds, 1 has the best docking scores against VEGFR1 (−11.744 kcal/mol), VEGFR2 (−12.407 kcal/mol) and EGFR (−10.359 kcal/mol). During MD simulations, compound 1 consistently exhibited strong hydrogen bond interactions with the active sites of VEGFR1 and 2, and these interactions were maintained for more than 90% of the simulation time. Additionally, the RMSD and RMSF values of the ligand–protein complexes exhibited high stability at their minimum levels around 1–2 Å. In conclusion, these findings suggest that compound 1 may be a potent and selective inhibitor candidate for lung cancer treatment and inhibition of VEGFR2, especially.

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Synthesis of novel 2-phenyl-3-[2-(substituted amino) ethylamino] quinazolin-4(3H)-ones as a new class of H1-antihistaminic agents

Cited by 4 publications

References 4 publications

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

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

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

A series of quinazolin‐4(3H)‐one‐morpholine hybrids as anti‐lung‐cancer agents: Synthesis, molecular docking, molecular dynamics, ADME prediction and biological activity studies

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