Apoptosis induction by 7-chloroquinoline-1,2,3-triazoyl carboxamides in triple negative breast cancer cells

作者：Begnini Karine Rech; Duarte Wladimir R; da Silva Liziane Pereira; Buss Julieti H; Goldani Bruna S; Fronza Mariana; Segatto Natalia Vieira; Alves Diego; Savegnago Lucielli; Seixas Fabiana Kommling; Collares Tiago^*

来源：Biomedicine & Pharmacotherapy, 2017, 91: 510-516.

DOI：10.1016/j.biopha.2017.04.098

• Quinoline derivatives
• 1,2,3 triazol
• Anticancer activity
• Breast cancer cytotoxicity

Breast cancer is a major public health burden in both developed and developing countries and there is still a need to screen new molecules with different modes of actions. The aims of this study were to evaluate the selectivity profile, apoptotic cell death and cell cycle arrest induced by 7-chloroquinoline1,2,3-triazoyl carboxamides derivatives in hormonal-dependent and hormonal-independent breast cancer cells. Results showed significantly decreased MCF-7 and MDA-MB-231 cells viability in vitro in a dose dependent manner after treatment with 7-chloroquinoline derivatives QTCA-1, QTCA-2 and QTCA-3. QTCA-1 displayed the highest cytotoxic activity from all the tested compounds in MDA-MB-231 with IC50 values of 20.60, 20.42 and 19.91 mu M in 24, 48 and 72 h of treatment respectively. Apoptosis induction was also significantly higher in the hormonal-independent breast cancer cells, with 80.4% of dead cells in MDA-MB-231 and only 16.8% of dead in MCF-7 cells. As a result, G0/G1 cycle arrest was observed in MCF-7 cells and no cell cycle arrest at all was observed in MDA-MB-231 cells. Molecular docking showed a high affinity of QTCA-1 to PARP-1, Scr and PI3K/mTOR targets. These results suggest a strong activity of the 7-chloroquinoline derivative QTCA-1 in independent-hormonal cells and suggest selectivity for triple negative cells.

• 出版日期2017-7