TY - JOUR
T1 - Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line
T2 - Quantitative Structure–Activity Relationship Models
AU - Mellado, Marco
AU - Madrid, Alejandro
AU - Reyna, Mauricio
AU - Weinstein-Oppenheimer, Caroline
AU - Mella, Jaime
AU - Salas, Cristian O.
AU - Sánchez, Elizabeth
AU - Cuellar, Mauricio
N1 - Funding Information:
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.
Funding Information:
We thank the Direcci?n de Investigaci?n y Postgrado (DGIP) of Universidad T?cnica Federico Santa Mar?a, scientific initiation project 2014 (PIIC-MM) and CONICYT Programa Formaci?n de Capital Humano Avanzado 21130456 and Fondecyt grants 1141264; 11130701 and Fondecyt Postdoctorado grant 3180408. Miss Ursula Mart?nez and Dr. Guillermo Diaz Fleming of Laboratorio de Espectroscop?a At?mica y Molecular (CESPAM), Universidad de Playa Ancha for technical support in infrared spectroscopy. The authors declare no conflict of interest.
Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
KW - 2D-QSAR
KW - Antiproliferative activity
KW - Cancer
KW - Chalcones
KW - Neuroblastoma
KW - SH-SY5Y
UR - http://www.scopus.com/inward/record.url?scp=85053624425&partnerID=8YFLogxK
U2 - 10.1007/s00044-018-2245-2
DO - 10.1007/s00044-018-2245-2
M3 - Article
AN - SCOPUS:85053624425
VL - 27
SP - 2414
EP - 2425
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
SN - 1054-2523
IS - 11-12
ER -