Synthesis of 2,4-disubstituted quinazolines promoted by deep eutectic solvent

Singh, Rajkumar Romeshkumar; Singh, T. K.; Devi, Th. Kanon; Devi, Thokchom Jeeta; Singh, Okram Mukherjee

doi:10.1016/j.crgsc.2021.100130

Cited by 6 publications

(1 citation statement)

References 29 publications

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“…They have demonstrated that DESs, particularly ChCl:urea (1:2), can significantly increase the yield of the ring closure. 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%