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Design, synthesis, antifungal activity, and structure–activity relationship studies of chalcones and hybrid dihydrochromane–chalcones

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Abstract

A series of ten chalcones (7a–j) and five new dihydrochromane–chalcone hybrids (7k–o) were synthesized and identified using spectroscopic techniques (IR, NMR, and MS). All compounds were evaluated in vitro against the B. cinerea and M. fructicola phytopathogens that affect a wide range of crops of commercial interest. All compounds were tested against both phytopathogens using the mycelial growth inhibition test, and it was found that two and five compounds had similar activity to that of the positive control for B. cinerea (7a = 43.9, 7c = 45.5, and Captan®= 24.8 µg/mL) and M. fructicola (7a = 48.5, 7d = 78.2, 7e = 56.1, 7f = 51.8, 7n = 63.2, and Mystic®= 21.6 µg/mL), respectively. To understand the key chalcone structural features for the antifungal activity on B. cinerea and M. fructicola, we developed structure–activity models with good statistical values (r2 and q2 higher than 0.8). For B. cinerea, the hydrogen bonding donor and acceptor and the atomic charge on C5 modulate the mycelial growth inhibition activity. In contrast, dipole moment and atomic charge on C1′ and the carbonyl carbon modify the inhibition activity for M. fructicola. These results allow the design of other compounds with activities superior to those of the compounds obtained in this study.

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Acknowledgements

The authors thank Vicerectoria de Investigación y Estudios Avanzados of Pontificia Universidad Católica de Valparaíso, and Dr. Carlos Echiburu-Chau for the collection and identification of S. graveolens.

Funding

This research was funded by CONICYT Programa Formación de Capital Humano Avanzado 21130456, Postdoctoral Fondecyt grant 3180408, and Vicerectoria de Investigación y Estudios Avanzados of Pontificia Universidad Católica de Valparaíso VRIEA-PUCV “37.0/2017”.

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Authors and Affiliations

  1. Facultad de Ciencias, Instituto de Química, Pontificia Universidad Católica de Valparaíso, Av. Universidad #330, Curauma, Valparaiso, Chile

    Marco Mellado

  2. Departamento de Química, Universidad Técnico Federico Santa María, Av. España 1680, Valparaiso, Chile

    Luis Espinoza & Katy Diaz

  3. Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Avda. Leopoldo Carvallo 270, Valparaiso, Chile

    Alejandro Madrid

  4. Facultad de Ciencias, Instituto de Química, Universidad de Valparaíso, Av. Gran Bretaña 1111, Valparaiso, Chile

    Jaime Mella

  5. Departamento Laboratorios y Estaciones Cuarentenarias, Servicio Agrícola y Ganadero, Ruta 68 #19100 (Km. 12), Pudahuel, Santiago, Chile

    Eduardo Chávez-Weisser

  6. Facultad de Farmacia, Centro de Investigación Farmacopea Chilena, Universidad de Valparaíso, Av. Gran Bretaña 1093, Valparaiso, Chile

    Mauricio Cuellar

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  1. Marco Mellado
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  2. Luis Espinoza
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  6. Katy Diaz
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  7. Mauricio Cuellar
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Contributions

KD was involved in design, evaluation, interpretation and discussion of biological activity, and manuscript redaction; AM wrote and proofread the manuscript; LE and MC were involved in spectroscopic analysis and discussion. JM was involved in 2D-QSAR models discussion; ECW isolated and identified M. fructicola; MM synthesized and isolated all compounds, was involved in spectroscopic analysis and discussion and development and analysis of 2D-QSAR models, and wrote and proofread the manuscript.

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Correspondence to Marco Mellado or Katy Diaz.

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Mellado, M., Espinoza, L., Madrid, A. et al. Design, synthesis, antifungal activity, and structure–activity relationship studies of chalcones and hybrid dihydrochromane–chalcones. Mol Divers 24, 603–615 (2020). https://doi.org/10.1007/s11030-019-09967-y

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