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

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

  • RSC Med Chem. 2024 Mar 19;15(4):1362-1380. doi: 10.1039/d3md00682d.
Luísa Carvalho 1 2,  Fábio Pedroso de Lima 3,  Mónica Cerqueira 1 2,  Ana Silva 1 2,  Olívia Pontes 1 2,  Sofia Oliveira-Pinto 1 2,  Sara Guerreiro 1 2 4,  Marta D Costa 1 2,  Sara Granja 1 2 4,  Patrícia Maciel 1 2,  Adhemar Longatto-Filho 1 2 5 6,  Fátima Baltazar 1 2,  Fernanda Proença 3,  Marta Costa 1 2
Affiliations

Affiliations

  • 1 Life and Health Sciences Research Institute (ICVS), University of Minho Campus of Gualtar Braga Portugal [email protected].
  • 2 ICVS/3B's - PT Government Associate Laboratory Braga/Guimarães Portugal.
  • 3 Department of Chemistry, University of Minho Campus of Gualtar Braga Portugal [email protected].
  • 4 Department of Pathological, Cytological and Thanatological Anatomy, School of Health, Polytechnic Institute of Porto 4200-072 Porto Portugal.
  • 5 Molecular Oncology Research Center, Barretos Cancer Hospital São Paulo Brazil.
  • 6 Medical Laboratory of Medical Investigation (LIM) 14, Department of Pathology, Medical School, University of São Paulo São Paulo Brazil.
PMID: 38665823 DOI: 10.1039/d3md00682d
Abstract

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.

Figures