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

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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.

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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.

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Authors and Affiliations

  1. Instituto de Química, Pontificia Universidad Católica de Valparaíso, Avenida Universidad 330, Valparaíso, Chile

    Marco Mellado

  2. Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Avenida Leopoldo Carvallo 270, Playa Ancha, Valparaíso, Chile

    Alejandro Madrid

  3. Escuela de Química y Farmacia, Facultad de Farmacia, Universidad de Valparaíso, Avenida Gran Bretaña 1093, Valparaíso, Chile

    Mauricio Reyna, Caroline Weinstein-Oppenheimer & Mauricio Cuellar

  4. Centro de Investigación Farmacopea Chilena, Universidad de Valparaíso, Santa Marta 183, Valparaíso, Chile

    Caroline Weinstein-Oppenheimer, Jaime Mella & Mauricio Cuellar

  5. Instituto de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Avenida Gran Bretaña 1111, Playa Ancha, Casilla 5030, Valparaíso, Chile

    Jaime Mella

  6. Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Avda. Av. Vicuña Mackenna 4860, Macul, Santiago, Chile

    Cristian O. Salas

  7. Centro de Biotecnología, Universidad Técnica Federico Santa María, Avenida España 1680, Valparaíso, Chile

    Elizabeth Sánchez

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  1. Marco Mellado
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  2. Alejandro Madrid
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  3. Mauricio Reyna
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  8. Mauricio Cuellar
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Correspondence to Marco Mellado or Mauricio Cuellar.

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Mellado, M., Madrid, A., Reyna, M. et al. Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line: Quantitative Structure–Activity Relationship Models. Med Chem Res 27, 2414–2425 (2018). https://doi.org/10.1007/s00044-018-2245-2

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