2. Academic Validation
  3. Novel naphthoquinone-1H-1,2,3-triazole hybrids: Design, synthesis and evaluation as inductors of ROS-mediated apoptosis in the MCF-7 cells

Novel naphthoquinone-1H-1,2,3-triazole hybrids: Design, synthesis and evaluation as inductors of ROS-mediated apoptosis in the MCF-7 cells

  • Bioorg Med Chem. 2024 Mar 15:102:117671. doi: 10.1016/j.bmc.2024.117671.
Acácio S de Souza 1,  Deborah S Dias 2,  Ruan C B Ribeiro 3,  Dora C S Costa 3,  Matheus G de Moraes 3,  David R Pinho 3,  Maria E G Masset 1,  Laís M Marins 3,  Sandy P Valle 3,  Cláudio J C de Carvalho 3,  Gustavo S G de Carvalho 3,  Angélica Lauria N Mello 2,  Mauro Sola-Penna 4,  Marcos V Palmeira-Mello 5,  Raissa A Conceição 5,  Carlos R Rodrigues 5,  Alessandra M T Souza 5,  Luana da S M Forezi 3,  Patricia Zancan 6,  Vitor F Ferreira 7,  Fernando de C da Silva 8
Affiliations

Affiliations

  • 1 Universidade Federal Fluminense, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, CEP 24241-000 Niterói, RJ, Brazil.
  • 2 Laboratório de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ CEP 21941-902, Brazil.
  • 3 Universidade Federal Fluminense, Departamento de Química Orgânica, Instituto de Química, Campus do Valonguinho, CEP 24020-150 Niterói, RJ, Brazil.
  • 4 Universidade Federal do Rio de Janeiro, Laboratório de Oncobiologia Molecular (LabOMol), Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, CEP 21941-902 Rio de Janeiro, RJ, Brazil.
  • 5 Laboratório de Modelagem Molecular & QSAR (ModMolQSAR), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ CEP 21941-590, Brazil.
  • 6 Laboratório de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ CEP 21941-902, Brazil. Electronic address: [email protected].
  • 7 Universidade Federal Fluminense, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, CEP 24241-000 Niterói, RJ, Brazil. Electronic address: [email protected].
  • 8 Universidade Federal Fluminense, Departamento de Química Orgânica, Instituto de Química, Campus do Valonguinho, CEP 24020-150 Niterói, RJ, Brazil. Electronic address: [email protected].
PMID: 38452407 DOI: 10.1016/j.bmc.2024.117671
Abstract

The search for novel Anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing Cancer research and enhancing patient outcomes in the battle against Cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for Cancer treatment. The antitumor activity of the novel compounds was tested using the breast Cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast Cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased Reactive Oxygen Species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.

Keywords

Anticancer; Breast cancer treatment; In silico toxicity; Mannich bases.

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