Synthesis of chalcones derived from 1-naphthylacetophenone and evaluation of their cytotoxic and apoptotic effects in acute leukemia cell lines
Authors: Natália Marcéli Stefanes
Ricardo José Nunes
Amanda Virtuoso Jacques
Ana Carolina Rabello de Moraes
Luiz Felipe Schmitz de Souza
Larissa Sens
Carolina Teixeira Martins
Stephanie Milis Syracuse
Luma Godoy Magalhaes
Fernanda da Luz Efe
Adriano Defini Andricopulo
Lisandra de Oliveira Silva
Daiane Mari Perondi
Laura Otto Walter
Maria Cláudia Santos-Silva
Aldo Sena de Oliveira
Journal: Bioorganic Chemistry (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Acute leukemia; Apoptosis; Chalcones; Cytotoxicity.
Affiliations: Laboratory of Experimental Oncology and Hemopathies, Department of Clinical Analysis, Florianópolis, Santa Catarina 88040-900, Brazil; Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil., Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil., Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil; Structure and Activity Laboratory, Department of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil., Department of Exact Sciences and Education, Federal University of Santa Catarina, Florianópolis, Santa Catarina 89036-002, Brazil; Laboratory of Medicinal and Computational Chemistry, Institute of Physics of São Carlos, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil., Laboratory of Medicinal and Computational Chemistry, Institute of Physics of São Carlos, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil., Laboratory of Experimental Oncology and Hemopathies, Department of Clinical Analysis, Florianópolis, Santa Catarina 88040-900, Brazil; Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil. Electronic address: .

Abstract:  Chalcones and their derivatives have been described as promising compounds with antiproliferative activity against leukemic cells. This study aimed to investigate the cytotoxic effect of three synthetic chalcones derived from 1-naphthylacetophenone (F07, F09, and F10) in acute leukemia cell lines (K562 and Jurkat) and examine the mechanisms of cell death induced by these compounds. The three compounds were cytotoxic to K562 and Jurkat cells, with IC50 values ranging from 1.03 to 31.66 µM. Chalcones induced intrinsic and extrinsic apoptosis, resulting in activation of caspase-3 and DNA fragmentation. F07, F09, and F10 were not cytotoxic to human peripheral blood mononuclear cells, did not produce any significant hemolytic activity, and did not affect platelet aggregation after ADP stimulation. These results, combined with calculations of molecular properties, suggest that chalcones F07, F09, and F10 are promising molecules for the development of novel antileukemic drugs. 

Retracted: No

PubPeer comments:
 Concern about Figure 6B. * The photo shown in the Jurkat panel appears to be a stretched version of the photo representing the K562 panel. ![file] ,