2. Academic Validation
  3. Batzelladine D and norbatzelladine L purified from marine sponge Monanchora arbuscula induce the reversal of fluconazole

Batzelladine D and norbatzelladine L purified from marine sponge Monanchora arbuscula induce the reversal of fluconazole

  • Bioorg Chem. 2020 Dec;105:104402. doi: 10.1016/j.bioorg.2020.104402.
Levy T S Domingos 1,  Mário F C Santos 2,  Daniel C de Moraes 1,  Leandro F R de Sá 1,  Vinicius A D da Silva 1,  Lana M Meuren 3,  Roberto G S Berlinck 2,  Antonio Ferreira-Pereira 4
Affiliations

Affiliations

  • 1 Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, Universidade Federal do Rio de Janeiro, CEP 21949-900 Rio de Janeiro, RJ, Brazil.
  • 2 Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970 São Carlos, SP, Brazil.
  • 3 Departamento de Virologia, IMPG, Universidade Federal do Rio de Janeiro, CEP 21949-900 Rio de Janeiro, RJ, Brazil.
  • 4 Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, Universidade Federal do Rio de Janeiro, CEP 21949-900 Rio de Janeiro, RJ, Brazil. Electronic address: apereira@micro.ufrj.br.
PMID: 33130347 DOI: 10.1016/j.bioorg.2020.104402
Abstract

ATP-Binding Cassette (ABC) transporters are the main class of transmembrane transporters involved in pathogenic Fungal resistance against chemotherapeutic agents. Herein we report results which show that batzelladine D (1) and norbatzelladine L (2) reverse the fluconazole resistance phenotype mediated by Pdr5p transporter on Saccharomyces cerevisiae. Both Alkaloids were able to chemosensitize the Pdr5p-overexpressing strain by synergistic interaction with fluconazole. Both compounds also showed an inhibitory effect on the catalytic activity and on the intracellular accumulation of rhodamine 6G, and did not show significant in vitro mammalian cells toxicity.

Keywords

ABC transporters; Batzelladines; Fluconazole resistance; Marine natural products; Marine sponges; Yeast.

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