Scholarlink

<p>The increase in fungal infections, the limited therapeutic arsenal, and the emergence of resistance pose a global health problem. <i>Candida</i> spp. stand out as opportunistic pathogens that cause superficial and invasive diseases. Thus, the search for new therapeutic alternatives, such as drug repositioning, is necessary. Duloxetine (DUL), a serotonin-norepinephrine reuptake inhibitor antidepressant used to treat depression, has demonstrated antifungal activity and potentiates the effects of conventional antifungals in vitro. The objective of this study is to evaluate the in vitro activity of duloxetine (DUL) against resistant <i>Candida</i> spp. strains. To this end, the minimum inhibitory concentration (MIC) of DUL alone and in combination with conventional antifungals was determined in order to evaluate the type of interaction between them, as well as the minimum fungicidal concentration (MFC). The activity of DUL against mature and developing biofilms was evaluated, in addition to the possible antifungal mechanism of action. DUL showed MICs of 16 to 128&#xa0;µg/mL with a fungicidal action profile, and when combined there was synergistic interaction with amphotericin B (AMB). In biofilms, DUL exhibited antibiofilm activity and enhanced AMB activity against developing, but not mature, biofilms. Mechanism of action analysis showed that DUL promoted oxidative stress, evidenced by increased reactive oxygen species (ROS) production, reduced GSH levels, mitochondrial depolarization, and phosphatidylserine externalization, suggesting the activation of the apoptotic pathway as a possible mechanism of cell death. The pro-oxidant effects of DUL were evident in <i>C. albicans</i> strains deficient in antioxidant defenses (<i>cap1Δ</i> and <i>gpx3Δ</i>) compared to the wild-type strain. DUL exhibited antibiofilm activity and enhanced AMB activity against developing, but not mature, biofilms.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Duloxetine repositioning: Investigation of antifungal and antibiofilm activity against fluconazole-sensitive and resistant Candida Spp. strains

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月3日

查看全文
  • Sarah Alves Barbosa,
  • Dávylla Rênnia Saldanha Pinheiro,
  • Leilson Carvalho de Oliveira,
  • Lara Elloyse de Almeida Moreira,
  • Vitória Pessoa de Farias Cabral,
  • Daniel Sampaio Rodrigues,
  • Beatriz Oliveira de Souza,
  • Hélio Vitoriano Nobre Júnior,
  • Livia Gurgel Do Amaral Valente Sa,
  • Bruno Coêlho Cavalcanti,
  • Islay Lima Magalhães,
  • José Roberto de Oliveira Ferreira,
  • Manoel Odorico de Moraes,
  • João Batista de Andrade Neto,
  • Cecília Rocha da Silva

摘要

The increase in fungal infections, the limited therapeutic arsenal, and the emergence of resistance pose a global health problem. Candida spp. stand out as opportunistic pathogens that cause superficial and invasive diseases. Thus, the search for new therapeutic alternatives, such as drug repositioning, is necessary. Duloxetine (DUL), a serotonin-norepinephrine reuptake inhibitor antidepressant used to treat depression, has demonstrated antifungal activity and potentiates the effects of conventional antifungals in vitro. The objective of this study is to evaluate the in vitro activity of duloxetine (DUL) against resistant Candida spp. strains. To this end, the minimum inhibitory concentration (MIC) of DUL alone and in combination with conventional antifungals was determined in order to evaluate the type of interaction between them, as well as the minimum fungicidal concentration (MFC). The activity of DUL against mature and developing biofilms was evaluated, in addition to the possible antifungal mechanism of action. DUL showed MICs of 16 to 128 µg/mL with a fungicidal action profile, and when combined there was synergistic interaction with amphotericin B (AMB). In biofilms, DUL exhibited antibiofilm activity and enhanced AMB activity against developing, but not mature, biofilms. Mechanism of action analysis showed that DUL promoted oxidative stress, evidenced by increased reactive oxygen species (ROS) production, reduced GSH levels, mitochondrial depolarization, and phosphatidylserine externalization, suggesting the activation of the apoptotic pathway as a possible mechanism of cell death. The pro-oxidant effects of DUL were evident in C. albicans strains deficient in antioxidant defenses (cap1Δ and gpx3Δ) compared to the wild-type strain. DUL exhibited antibiofilm activity and enhanced AMB activity against developing, but not mature, biofilms.