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Synthesis and biological evaluation of novel chromonyl enaminones as α-glucosidase inhibitors

  • Aarón Mendieta-MoctezumaEmail author
  • Catalina Rugerio-Escalona
  • Nemesio Villa-Ruano
  • Rsuini U. Gutierrez
  • Fabiola E. Jiménez-Montejo
  • M. Jonathan Fragoso-Vázquez
  • José Correa-Basurto
  • María C. Cruz-López
  • Francisco Delgado
  • Joaquín TamarizEmail author
Original research
  • 44 Downloads

Abstract

Series of novel chromonyl enaminones 1a–e and 2ae and 3-alkylated chromones 3ae were synthesized and evaluated in vitro as α-glucosidase inhibitors as well as antioxidant and antifungal agents. Antifungal activity was tested on strains of Candida albicans. Compounds 2a and 2de showed good inhibition of the α-glucosidase enzyme (IC50 = 5.5, 0.9, and 1.5 mM, respectively), their effect being better than that of 1ae, 3ae, and acarbose (the standard, IC50 = 7.73 ± 0.9 mM). The structure–activity relationship suggests that the phenyl group at the C-3 position of the chromone ring system and the 4-chlorophenyl group at the enaminone moiety (derivatives 2) increased the inhibition of α-glucosidase. Compounds 2ae exhibited a slight antioxidant effect, and compounds 3ae a moderate antifungal activity against C. albicans (IC50 70.5–83.1 µg/mL). Docking studies revealed that compounds 2 interact with the α-glucosidase residues of the binding pocket. Therefore, these chromone derivatives may be considered as potential α-glucosidase inhibitors, as well as antifungal agents against some Candida strains of yeast.

Keywords

Chromonyl enaminones Chromones α-glucosidase inhibitors Candida albicans 

Notes

Acknowledgements

The authors thank Carlos Espinoza-Hicks for help in spectrometric measurements and Bruce A. Larsen for proofreading. J.T. acknowledges financial support from the Secretaría de Investigación y Posgrado, Instituto Politécnico Nacional (SIP-IPN) (grants 20090326, 20100236, 20110172, 20120830, 20130686, 20140858, 20180198, and 20195228) and CONACYT (grants 83446 and 178319). For financial support, F.D. is grateful to SIP-IPN (grants 20170925, 20181332, and 20195287) and J.C.-B. to CONACyT (CBB-254600 and APN-782). A.M.-M. and C.R.-E. thank CONACYT for the graduate scholarships awarded (178319 and 264517) and SIP-IPN (BEIFI) for a complementary scholarship. This work was financially supported by a project from SIP-IPN (20170430, 20181433, 20195786). F.E.J.-M. (20160247), M.C.C.-L. (20160206), F.D., and J.T. are fellows of the Estímulos al Desempeño de los Investigadores (EDI-IPN), and M.C.C.-L., F.D., and J.T. are fellows of the Comisión de Operación y Fomento de Actividades Académicas (COFAA)-IPN.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2320_MOESM1_ESM.doc (12.5 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Aarón Mendieta-Moctezuma
    • 1
    • 2
    Email author
  • Catalina Rugerio-Escalona
    • 1
  • Nemesio Villa-Ruano
    • 3
  • Rsuini U. Gutierrez
    • 2
  • Fabiola E. Jiménez-Montejo
    • 1
  • M. Jonathan Fragoso-Vázquez
    • 4
  • José Correa-Basurto
    • 4
  • María C. Cruz-López
    • 1
  • Francisco Delgado
    • 2
  • Joaquín Tamariz
    • 2
    Email author
  1. 1.Centro de Investigación en Biotecnología Aplicada, Instituto Politécnico NacionalCarretera Estatal Santa Inés Tecuexcomac-TepetitlaTlaxcalaMexico
  2. 2.Departamento de Química Orgánica, Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalCiudad de MéxicoMexico
  3. 3.Universidad de la Sierra SurCiudad UniversitariaOaxacaMexico
  4. 4.Laboratorio de Desarrollo de Fármacos y Productos Biotecnológicos, Escuela Superior de MedicinaInstituto Politécnico NacionalCiudad de MéxicoMexico

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