Synthesis of chalcones derived from 1-naphthylacetophenone and evaluation of their cytotoxic and apoptotic effects in acute leukemia cell lines.

Autor: Jacques AV; 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., Stefanes NM; 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., Walter LO; 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., Perondi DM; 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., Efe FDL; Post-Graduation Program in Pharmacy, Health Science Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88040-900, Brazil., de Souza LFS; 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., Sens L; 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., Syracuse SM; 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., de Moraes ACR; 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., de Oliveira AS; 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., Martins CT; Laboratory of Medicinal and Computational Chemistry, Institute of Physics of São Carlos, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil., Magalhaes LG; Laboratory of Medicinal and Computational Chemistry, Institute of Physics of São Carlos, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil., Andricopulo AD; Laboratory of Medicinal and Computational Chemistry, Institute of Physics of São Carlos, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil., Silva LO; 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., Nunes RJ; 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., Santos-Silva MC; 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: maria.claudia.silva@ufsc.br.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2021 Nov; Vol. 116, pp. 105315. Date of Electronic Publication: 2021 Sep 01.
DOI: 10.1016/j.bioorg.2021.105315
Abstrakt: 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 IC 50 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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