Green chemistry approach to the synthesis of 3-substituted-quinazolin-4(3<i>H</i>)-ones and 2-methyl-3-substituted-quinazolin-4(3<i>H</i>)-ones and biological evaluation

Komar, Mario; Molnar, Maja; Jukić, Marijana; Glavaš‐Obrovac, Ljubica; Opačak-Bernardi, Teuta

doi:10.1080/17518253.2020.1741694

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…59 Also, it has been shown that L-(+)-Tartaric acid and N, N'-Dimethylurea (DMU) as a DES have a significant impact on the yield of quinazolinone synthesis. 60 Similarly, Komar et al 61 have conducted a research on the synthesis of 3-Substituted-quinazolin-4(3H)-ones using ChCl:urea and their results have indicated that DES can be a convenient solvent for this type of the reaction.…”

Section: Resultsmentioning

confidence: 99%

Application of a Deep Eutectic Solvent for the Synthesis of Novel Imidazole-Containing Quinazoline Derivatives as Potent Cytotoxic Agents

Azmian Moghadam,

Dabirian,

Ebrahimi Tavani

et al. 2024

Pharm Sci

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Background: Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents. Methods: All final compounds were synthesized using two methods, including a conventional approach using potassium iodide and dimethylformamide as well as a green method using a deep eutectic solvent (DES) comprising choline chloride: urea. The cytotoxicity was tested on the A431, HUVEC, and HU02 cell lines. To evaluate the binding pattern of the compounds with EGFR and VEGFR-2, a molecular docking investigation was performed. Finally, the wound healing assay was carried out to assess the potency of compounds in inhibiting cell migration. Results: The final reaction time was approximately 15-20 min with yields of 60-72% using DES, while the conventional method took 3 to 4 h to complete, with yields between 30% and 42%. Compounds 8k and 8l showed better cytotoxicity against both cell lines compared to vandetanib (IC50=0.11 µM and 0.26 µM on A431 and IC50=5.01 µM and 5.24 µM on HUVEC, respectively). Molecular docking studies revealed that compound 8k, which contained 3-methylaniline at the 4-position of the quinazoline core, showed efficient binding affinity to both EGFR and VEGFR-2. An essential hydrogen bond was formed between quinazoline N1 of 8k and the Met796 residue of EGFR with a docking score of -8.76 kcal/mol. The imidazole N3 of 8k interacted with the Cyc919 residue of VEGFR-2, forming a hydrogen bond with a docking score of -9.03 kcal/mol. Moreover, compound 8k exhibited the best inhibitory activity on cell migration and wound healing. Conclusion: DES significantly improved the time and yield of the final reactions. Compound 8k, which showed the best cytotoxicity and inhibitory activity on cell migration, could be a suitable candidate for further structural optimization.

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Section: Resultsmentioning

confidence: 99%

Application of a Deep Eutectic Solvent for the Synthesis of Novel Imidazole-Containing Quinazoline Derivatives as Potent Cytotoxic Agents

Azmian Moghadam,

Dabirian,

Ebrahimi Tavani

et al. 2024

Pharm Sci

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“…Choline chloride-based DESs have been in focus of our investigation for some time, and we found them to be suitable for different chemical processes, both heterocyclic compounds synthesis [17,25,33,43] and extraction [44]. In this regard, the objectives of this research were focused on the investigation on finding an appropriate Type III [36], choline chloride-based deep eutectic (ChCl-based DES) solvent for the synthesis of 3-substituted 2-mercaptoquinazolin-4(3H)-one derivatives, as well as on the influence of some reaction parameters such as temperature and reaction time.…”

Section: Resultsmentioning

confidence: 99%

“…There are many different methods for preparing these extensively studied heterocyclic compounds. Among them, the main synthetic routes use anthranilic acid [15][16][17][18][19], anthranilate [20], isatoic anhydride [21][22][23], benzoxazinone [24][25][26][27] and 2-iodoaniline [28] as convenient precursors. For preparation of 2-mercaptoquinazolinone derivatives, anthranilic acid is the most common starting material.…”

Section: Introductionmentioning

confidence: 99%

Application of Deep Eutectic Solvents in the Synthesis of Substituted 2-Mercaptoquinazolin-4(3H)-Ones: A Comparison of Selected Green Chemistry Methods

et al. 2022

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In this study, deep eutectic solvents (DESs) were used as green and eco-friendly media for the synthesis of substituted 2-mercaptoquinazolin-4(3H)-ones from different anthranilic acids and aliphatic or aromatic isothiocyanates. A model reaction on anthranilic acid and phenyl isothiocyanate was performed in 20 choline chloride-based DESs at 80 °C to find the best solvent. Based on the product yield, choline chloride:urea (1:2) DES was found to be the most effective, while DESs acted both as solvents and catalysts. Desired compounds were prepared with moderate to good yields using stirring, microwave-assisted, and ultrasound-assisted synthesis. Significantly, higher yields were obtained with mixing and ultrasonication (16–76%), while microwave-induced synthesis showed lower effectiveness (13–49%). The specific contribution of this research is the use of DESs in combination with the above-mentioned green techniques for the synthesis of a wide range of derivatives. The structures of the synthesized compounds were confirmed by 1H and 13C NMR spectroscopy.

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“…Moreover, 3-substituted-quinazolin-4(3H)-one derivatives were prepared by Kom et al [47], using ChCl/urea eutectic solvent, in a two-step cyclization reacti Quinazolinones are a class of six-membered heterocycles exhibiting a range significant pharmacological properties, including antitumor activities [48]. In particu for the synthesis of 2-methyl-3-substituted-quinazolin-4(3H)-ones 62, at first, preparation of benzoxazinone 61, as an intermediate, starting from anthranilic acid and acetic anhydride, was carried out.…”

Section: For Peer Review 12 Omentioning

confidence: 99%

“…Afterwards, benzoxazinone 61 and a prim amine were added to the ChCl-based DES, affording, under heating at 80 °C, corresponding benzo-fused derivatives 62 in 53-84% yield (Scheme 20). A dual role the DES, as both the green medium and catalyst, through the formation of hydrog bonds with the reactants and reaction intermediates, was hypothesized [47]. Moreover, 3-substituted-quinazolin-4(3H)-one derivatives were prepared by Komar et al [47], using ChCl/urea eutectic solvent, in a two-step cyclization reaction.…”

Section: For Peer Review 12 Omentioning

confidence: 99%

N-, O- and S-Heterocycles Synthesis in Deep Eutectic Solvents

et al. 2023

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The synthesis of heterocycles is a fundamental area of organic chemistry that offers enormous potential for the discovery of new products with important applications in our daily life such as pharmaceuticals, agrochemicals, flavors, dyes, and, more generally, engineered materials with innovative properties. As heterocyclic compounds find application across multiple industries and are prepared in very large quantities, the development of sustainable approaches for their synthesis has become a crucial objective for contemporary green chemistry committed to reducing the environmental impact of chemical processes. In this context, the present review focuses on the recent methodologies aimed at preparing N-, O- and S-heterocyclic compounds in Deep Eutectic Solvents, a new class of ionic solvents that are non-volatile, non-toxic, easy to prepare, easy to recycle, and can be obtained from renewable sources. Emphasis has been placed on those processes that prioritize the recycling of catalyst and solvent, as they offer the dual benefit of promoting synthetic efficiency while demonstrating environmental responsibility.

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Green chemistry approach to the synthesis of 3-substituted-quinazolin-4(3H)-ones and 2-methyl-3-substituted-quinazolin-4(3H)-ones and biological evaluation

Abstract: Teuta Opačak-Bernardi (2020) Green chemistry approach to the synthesis of 3-substitutedquinazolin-4(3H)-ones and 2-methyl-3-substituted-quinazolin-4(3H)-ones and biological evaluation,

Cited by 8 publications

References 38 publications

Application of a Deep Eutectic Solvent for the Synthesis of Novel Imidazole-Containing Quinazoline Derivatives as Potent Cytotoxic Agents

Application of a Deep Eutectic Solvent for the Synthesis of Novel Imidazole-Containing Quinazoline Derivatives as Potent Cytotoxic Agents

Application of Deep Eutectic Solvents in the Synthesis of Substituted 2-Mercaptoquinazolin-4(3H)-Ones: A Comparison of Selected Green Chemistry Methods

N-, O- and S-Heterocycles Synthesis in Deep Eutectic Solvents

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