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Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines-From the Synthesis to 3D-Cell Culture Effects.
da Gama Oliveira, Vanessa; Muxfeldt, Marcelly; Muniz da Paz, Mariana; Silva Coutinho, Mayra; Eduardo Dos Santos, Raissa; Diniz da Silva Ferretti, Giulia; Ferraz da Costa, Danielly C; Fonseca Regufe, Pedro; Lelis Gama, Ivson; da Costa Santos Boechat, Fernanda; Silva Lima, Emersom; Ferreira, Vitor Francisco; de Moraes, Marcela Cristina; Bastos Vieira de Souza, Maria Cecília; Netto Batalha, Pedro; Pereira Rangel, Luciana.
Afiliación
  • da Gama Oliveira V; Instituto Nacional de Infectologia, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, RJ, Brazil.
  • Muxfeldt M; Instituto de Química, Universidade Federal Fluminense, Niteroi 24020-141, RJ, Brazil.
  • Muniz da Paz M; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
  • Silva Coutinho M; Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus 69067-005, AM, Brazil.
  • Eduardo Dos Santos R; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
  • Diniz da Silva Ferretti G; Instituto de Química, Universidade Federal Fluminense, Niteroi 24020-141, RJ, Brazil.
  • Ferraz da Costa DC; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
  • Fonseca Regufe P; Instituto de Bioquimica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
  • Lelis Gama I; Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-013, RJ, Brazil.
  • da Costa Santos Boechat F; Instituto de Química, Universidade Federal Fluminense, Niteroi 24020-141, RJ, Brazil.
  • Silva Lima E; Instituto de Química, Universidade Federal Fluminense, Niteroi 24020-141, RJ, Brazil.
  • Ferreira VF; Faculdade da Amazônia Legal, Colider 78500-000, MT, Brazil.
  • de Moraes MC; Instituto de Química, Universidade Federal Fluminense, Niteroi 24020-141, RJ, Brazil.
  • Bastos Vieira de Souza MC; Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus 69067-005, AM, Brazil.
  • Netto Batalha P; Faculdade de Farmácia, Universidade Federal Fluminense, Niteroi 24020-141, RJ, Brazil.
  • Pereira Rangel L; Instituto de Química, Universidade Federal Fluminense, Niteroi 24020-141, RJ, Brazil.
Int J Mol Sci ; 25(12)2024 Jun 12.
Article en En | MEDLINE | ID: mdl-38928197
ABSTRACT
Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC50 values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Naftoquinonas / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Brasil

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Naftoquinonas / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Brasil