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Medicinal Chemistry Research

, Volume 27, Issue 11–12, pp 2414–2425 | Cite as

Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line: Quantitative Structure–Activity Relationship Models

  • Marco Mellado
  • Alejandro Madrid
  • Mauricio Reyna
  • Caroline Weinstein-Oppenheimer
  • Jaime Mella
  • Cristian O. Salas
  • Elizabeth Sánchez
  • Mauricio Cuellar
Original Research
  • 78 Downloads

Abstract

Chalcones are a group of molecules with a broad spectrum of biological activities, being especially appealing for their antiproliferative effects on several cancer cell lines. For this reason, we synthesized 23 chalcones with good to excellent yields and assessed their effect on the viability of the SH-SY5Y neuroblastoma cell line and on primary human fibroblasts. The results indicated that 18 of these compounds were more active than 5-fluorouracil in the cancer cell line and one of them was more selective than this reference drug. To identify structural features related to the antiproliferative activity of these compounds, as well as, the selectivity on the cancer cell line, a 2D-QSAR analysis was performed. The QSAR model (q2 = 0.803; r2 = 0.836) showed that lipophilicity (CLogP) is the most important factor to increase their cytotoxicity on the cancer cell line. On the other hand, the selectivity QSAR model (q2 = 0.917; r2 = 0.916) showed that changes in the Mulliken’s charge of the carbonyl group and at the C4’ position in the chalcone core can increase the selectivity for SH-SY5Y cell line compared to normal fibroblasts.

Keywords

Chalcones Antiproliferative activity 2D-QSAR SH-SY5Y Cancer Neuroblastoma 

Notes

Acknowledgements

We thank the Dirección de Investigación y Postgrado (DGIP) of Universidad Técnica Federico Santa María, scientific initiation project 2014 (PIIC-MM) and CONICYT Programa Formación de Capital Humano Avanzado 21130456 and Fondecyt grants 1141264; 11130701 and Fondecyt Postdoctorado grant 3180408. Miss Ursula Martínez and Dr. Guillermo Diaz Fleming of Laboratorio de Espectroscopía Atómica y Molecular (CESPAM), Universidad de Playa Ancha for technical support in infrared spectroscopy.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

44_2018_2245_MOESM1_ESM.docx (8.1 mb)
Supplementary information

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Instituto de QuímicaPontificia Universidad Católica de ValparaísoValparaísoChile
  2. 2.Departamento de Química, Facultad de Ciencias Naturales y ExactasUniversidad de Playa AnchaValparaísoChile
  3. 3.Escuela de Química y Farmacia, Facultad de FarmaciaUniversidad de ValparaísoValparaísoChile
  4. 4.Centro de Investigación Farmacopea ChilenaUniversidad de ValparaísoValparaísoChile
  5. 5.Instituto de Química y Bioquímica, Facultad de CienciasUniversidad de ValparaísoValparaísoChile
  6. 6.Departamento de Química Orgánica, Facultad de QuímicaPontificia Universidad Católica de ChileSantiagoChile
  7. 7.Centro de BiotecnologíaUniversidad Técnica Federico Santa MaríaValparaísoChile

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