Your browser doesn't support javascript.
loading
Discovery of a new dihydroeugenol-chalcone hybrid with cytotoxic and anti-migratory potential: A dual-action hit for cancer therapeutics.
Nakao, Izadora Amaral; Almeida, Tamires Cunha; Cardoso Reis, Adriana Cotta; Coutinho, Gabrielly Guimarães; Hermenegildo, Aline Mol; Cordeiro, Cleydson Finotti; da Silva, Glenda Nicioli; Dias, Danielle Ferreira; Brandão, Geraldo Célio; Pinto Braga, Saulo Fehelberg; de Souza, Thiago Belarmino.
Afiliação
  • Nakao IA; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • Almeida TC; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • Cardoso Reis AC; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • Coutinho GG; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • Hermenegildo AM; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • Cordeiro CF; Pharmaceutical Sciences Faculty, Federal University of Alfenas, 37130-001 Alfenas, MG, Brazil.
  • da Silva GN; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • Dias DF; Institute of Chemistry, Federal University of Alfenas, 37130-001 Alfenas, MG, Brazil.
  • Brandão GC; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • Pinto Braga SF; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil.
  • de Souza TB; School of Pharmacy - Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil. Electronic address: thiago.souza@ufop.edu.br.
Bioorg Med Chem ; 96: 117516, 2023 12 15.
Article em En | MEDLINE | ID: mdl-37944413
Cancer still represents a serious public health problem and one of the main problems related to the worsening of this disease is the ability of some tumors to develop metastasis. In this work, we synthesized a new series of chalcones and isoxazoles derived from eugenol and analogues as molecular hybrids and these compounds were evaluated against different tumor cell lines. This structural pattern was designed considering the cytotoxic potential already known for eugenol, chalcones and isoxazoles. Notably, chalcones 7, 9, 10, and 11 displayed significant activity (4.2-14.5 µM) against two cancer cell lines, surpassing the potency of the control drug doxorubicin. The reaction of chalcones with hydroxylamine hydrochloride provided the corresponding isoxazoles that were inactive against these cancer cells. The dihydroeugenol chalcone 7 showed the most promising results, demonstrating higher potency against HepG2 (CC50: 4.2 µM) and TOV-21G (CC50: 7.2 µM). Chalcone 7 was also three times less toxic than doxorubicin considering HepG2 cells, with a selectivity index greater than 11. Further investigations including clonogenic survival, cell cycle progression and cell migration assays confirmed the compelling antitumoral potential of chalcone 7, as it reduced long-term survival due to DNA fragmentation, inducing cell death and inhibiting HepG2 cells migration. Moreover, in silico studies involving docking and molecular dynamics revealed a consistent binding mode of chalcone 7 with metalloproteinases, particularly MMP-9, shedding light on its potential mechanism of action related to anti-migratory effects. These significant findings suggest the inclusion of compound 7 as a promising candidate for future studies in the field of cancer therapeutics.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Chalcona / Chalconas / Neoplasias / Antineoplásicos Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Chalcona / Chalconas / Neoplasias / Antineoplásicos Idioma: En Ano de publicação: 2023 Tipo de documento: Article