2. Academic Validation
  3. Effects of β-lapachone and β-nor-lapachone on multidrug efflux transporters and biofilms of Candida glabrata

Effects of β-lapachone and β-nor-lapachone on multidrug efflux transporters and biofilms of Candida glabrata

  • Bioorg Med Chem. 2022 Jun 1;63:116749. doi: 10.1016/j.bmc.2022.116749.
Daniel Clemente de Moraes 1,  Maria do Carmo Freire Ribeiro Pinto 2,  Levy Tenório Sousa Domingos 1,  Victor do Valle Pereira Midlej 3,  Antônio Ferreira-Pereira 4
Affiliations

Affiliations

  • 1 Avenida Carlos Chagas Filho 373, Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, RJ CEP: 21941-590, Brazil.
  • 2 Avenida Carlos Chagas Filho 373, Laboratório de Química Heterocíclica, Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, RJ CEP: 21941-590, Brazil.
  • 3 Avenida Brasil 4365, Laboratório de Ultraestrutura Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ CEP: 21040-900, Brazil.
  • 4 Avenida Carlos Chagas Filho 373, Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, RJ CEP: 21941-590, Brazil. Electronic address: [email protected].
PMID: 35436747 DOI: 10.1016/j.bmc.2022.116749
Abstract

Infections caused particularly by Candida glabrata are hard to treat due to the development of Antifungal resistance that occurs mainly through the production of efflux pumps and biofilm. Thus, a promising strategy to overcome infections caused by C. glabrata could be to use a substance able to inhibit efflux pumps and eradicate biofilms. Lapachones are natural naphthoquinones that possess a variety of pharmacological properties. Previous studies show that these substances inhibit the growth, virulence factors and efflux pumps of C. albicans. The aim of the present study was to evaluate whether lapachones are able to inhibit efflux pumps related to Antifungal resistance in C. glabrata and either prevent biofilm formation or affect mature biofilms. Assays were performed with Saccharomyces cerevisiae strains that overexpress C. glabrata transporters (CgCdr1p and CgCdr2p). One C. glabrata clinical isolate that overexpresses CgCdr1p was also used. Both β-lapachone and β-nor-lapachone affected the growth of S. cerevisiae and C. glabrata when combined to fluconazole, and this action was inhibited by ascorbic acid. Both lapachones stimulated ROS production, inhibited efflux activity, adhesion, biofilm formation and the metabolism of mature biofilms of C. glabrata. Data obtained on the present study point to the potential use of β-lapachone and β-nor-lapachone as antibiofilm agents and adjuvants on the Antifungal therapy related to resistant infections caused by C. glabrata.

Keywords

ABC transporters; Biofilm; Candida glabrata; Fluconazole resistance; Lapachone; Quinones.

Figures
Products