In vitro and in vivo evaluation of novel chromeno[2,3-d]pyrimidinones as therapeutic agents for triple negative breast cancer

被引:0
作者
Carvalho, Luisa [1 ,2 ]
de Lima, Fabio Pedroso [3 ]
Cerqueira, Monica [1 ,2 ]
Silva, Ana [1 ,2 ]
Pontes, Olivia [1 ,2 ]
Oliveira-Pinto, Sofia [1 ,2 ]
Guerreiro, Sara [1 ,2 ,4 ]
Costa, Marta D. [1 ,2 ]
Granja, Sara [1 ,2 ,4 ]
Maciel, Patricia [1 ,2 ]
Longatto-Filho, Adhemar [1 ,2 ,5 ,6 ]
Baltazar, Fatima [1 ,2 ]
Proenca, Fernanda [3 ]
Costa, Marta [1 ,2 ]
机构
[1] Univ Minho, Life & Hlth Sci Res Inst ICVS, Campus Gualtar, Braga, Portugal
[2] ICVS 3Bs PT Govt Associate Lab, Braga Guimaraes, Portugal
[3] Univ Minho, Dept Chem, Campus Gualtar, Braga, Portugal
[4] Polytech Inst Porto, Sch Hlth, Dept Pathol Cytolog & Thanatol Anat, P-4200072 Porto, Portugal
[5] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil
[6] Univ Sao Paulo, Med Sch, Dept Pathol, Med Lab Med Invest LIM 14, Sao Paulo, Brazil
关键词
C-ELEGANS; MODEL; EXPRESSION; APOPTOSIS; TARGETS; MOUSE; CELLS;
D O I
10.1039/d3md00682d
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the limited therapeutic options show poor efficacy in patients, associated to severe side effects and development of resistance. Considering that chromene-based scaffolds proved to be attractive candidates for cancer therapy, herein we prepared new chromeno[2,3-d]pyrimidinone derivatives by a simple two step procedure, starting from the reaction of cyanoacetamide and a salicylaldehyde. A cell viability screening in several breast cancer cell lines allowed to identify two promising compounds with IC50 values in the low micromolar range for TNBC cells. These chromenes inhibited cell proliferation, induced cell cycle arrest and triggered cell death through apoptosis. In vivo studies revealed a safe profile in invertebrate and vertebrate animal models and confirmed their capacity to inhibit tumor growth in the CAM model, inducing significant tumor regression after 4 days of treatment. The two compounds identified in this study are promising drug candidates for TNBC treatment and valuable hits for future optimization, using the versatile synthetic platform that was developed.
引用
收藏
页码:1362 / 1380
页数:19
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