New chalcone-type compounds and 2-pyrazoline derivatives: synthesis and caspase-dependent anticancer activity

Authors and affiliations:
Artur Silva - Departamento de Química, Universidade de Aveiro; David Pereira - Faculdade de Farmácia, Universidade do Porto; Patrícia Valentão - Faculdade de Farmácia, Universidade do Porto; Paula Andrade - Faculdade de Farmácia, Universidade do Porto

Abstract:
Aim: There is a continuous and urgent need for new anticancer agents with novel structures and target selectivity. Methods & results: The anticancer activity of the prepared compounds was assessed against human lung (A549) and stomach (AGS) cancer cell lines and evaluated in the noncancer human lung fibroblast (MRC-5) cell line. 2-Pyrazolines were devoid of toxicity in all cell lines used, chalcones bearing a β-(benz)imidazole moiety being toxic toward AGS cell line. Mechanistic studies showed that these compounds trigger loss of cell viability and mitochondrial membrane potential, while eliciting morphological traits compatible with regulated cell death, which was ultimately shown to derive from caspase activation, specifically caspase-3. Conclusion: Chalcones 1-3 have been identified as new and promising anticancer agents toward the AGS cell line.

Journal: Future Medicinal Chemistry

Link: https://www.ncbi.nlm.nih.gov/pubmed/32100558