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Synthesis, biological evaluation and molecular docking of 3-substituted quinazoline-2,4(1H, 3H)-diones

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Abstract

The quinazoline-2,4-diones scaffold is found in bioactive compounds, commercial drugs and exhibit important biological activities. However, their antidiabetic activity is rarely explored. For this purpose, an easy one-pot three-components and straightforward synthesis of 3-substituted quinazoline-2,4-diones was designed, in both, the catalyst- and solvent-free conditions under microwave irradiation. Additionally, the synthesized compounds were screened for in vitro α-amylase and α-glucosidase inhibitory activity, as well as antioxidants and cytotoxicity. The quinazoline-2,4-diones were isolated, with yields in the range of 30-65%. The compounds 3d, 3e, 3g and 3h displayed moderate activity against α-amylase and/or α-glucosidase enzymes compared with the acarbose drug. The molecular docking study revealed that all active compounds displayed a different type of intermolecular interaction in the pocked site of these enzymes. Interestingly, in the Artemia salina assay, the compound 3d exhibited a higher cytotoxic effect than 5-fluorouracil. All these results support the pharmacological potential of quinazoline-2,4-diones since all evaluated compounds behave as moderate inhibitors of the enzymes α-amylase and/or α-glucosidase.

Graphic abstract

An easy one-pot three-components and straightforward synthesis of 3-substituted quinazoline-2,4-diones was designed, in both, the catalyst- and solvent-free conditions under microwave irradiation. Moreover, the in vitro α-amylase and α-glucosidase inhibitory activity, as well as antioxidants and cytotoxicity are reported.

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Acknowledgements

We gratefully acknowledge support for this project by Consejo Nacional de Ciencia y Tecnología (SEP-CONACyT, GRANT No CB-2012-178266-Q) and Programa de Fomento y Apoyo a Proyectos de Investigación (PROFAPI2014/206) of the Universidad Autónoma de Sinaloa.

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Author notes

  1. Ulises Osuna-Martínez and Juan I Sarmiento-Sánchez have contributed equally to this work.

Authors and Affiliations

  1. Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Sinaloa, Blvd. de las américas S/N, Campus Culiacán, 80040, Culiacán, Sinaloa, México

    Lumadhar Santos-Ballardo, Lorenzo A Picos-Corrales, Guadalupe Rendón-Maldonado & Ulises Osuna-Martínez

  2. Facultad de Ingeniería Culiacán, Universidad Autónoma de Sinaloa, Blvd. de las américas S/N, 80040, Culiacán, Sinaloa, México

    Fernando García-Páez & Juan I Sarmiento-Sánchez

  3. Tecnológico Nacional de México / IT de Tijuana, Blvd. Alberto Limón Padilla S/N, Mesa de Otay, 22500, Tijuana, BC, México

    Adrián Ochoa-Terán

  4. Laboratorio de Análisis de Residuos de Plaguicidas, Centro de Investigación en Alimentación y Desarrollo A.C., Carretera a El Dorado Km 5.5, Campo El Diez, 80129, Culiacán, Sinaloa, México

    Pedro Bastidas

  5. Facultad de Biología, Universidad Autónoma de Sinaloa, Blvd. de las américas S/N, Campus Culiacán, 80040, Culiacán, Sinaloa, México

    Loranda Calderón-Zamora

Authors
  1. Lumadhar Santos-Ballardo
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  2. Fernando García-Páez
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  3. Lorenzo A Picos-Corrales
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  4. Adrián Ochoa-Terán
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  6. Loranda Calderón-Zamora
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  7. Guadalupe Rendón-Maldonado
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  8. Ulises Osuna-Martínez
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  9. Juan I Sarmiento-Sánchez
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Correspondence to Ulises Osuna-Martínez or Juan I Sarmiento-Sánchez.

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Santos-Ballardo, L., García-Páez, F., Picos-Corrales, L.A. et al. Synthesis, biological evaluation and molecular docking of 3-substituted quinazoline-2,4(1H, 3H)-diones. J Chem Sci 132, 100 (2020). https://doi.org/10.1007/s12039-020-01813-1

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