Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, Universidade Federal do Rio de Janeiro, CEP 21949-900 Rio de Janeiro, RJ, Brazil.
Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970 São Carlos, SP, Brazil.
Bioorg Chem. 2020 Dec;105:104402. doi: 10.1016/j.bioorg.2020.104402. Epub 2020 Oct 21.
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.
三磷酸腺苷结合盒（ABC）转运蛋白是参与致病真菌对抗化学治疗药物的主要跨膜转运蛋白。本文报道 batzelladine D（1）和 norbatzelladine L（2）可逆转 Pdr5p 转运蛋白介导的氟康唑耐药表型的结果。这两种生物碱均能通过与氟康唑的协同作用使 Pdr5p 过表达菌株对化疗药物敏感。这两种化合物还显示出对催化活性和细胞内罗丹明 6G 积累的抑制作用，并且在体外哺乳动物细胞毒性方面没有显著作用。
