flunarizine  (MedChemExpress)

Journal: Frontiers in Pharmacology

Article Title: Myriocin enhances the antifungal activity of fluconazole by blocking the membrane localization of the efflux pump Cdr1

doi: 10.3389/fphar.2022.1101553

Figure Lengend Snippet: The impaired calcineurin signal pathway did not affect the function of Cdr1. (A) The sensitivities of C. albicans wild-type strain (SN152) and mutants (P ADH1 - CDR1 , cmp1 ∆/ cmp1 ∆, cmp1 ∆/ cmp1 ∆:: P ADH1 - CDR1 , crz1 ∆/ crz1 ∆, crz1 ∆/ crz1 ∆:: P ADH1 - CDR1 , rta2 ∆/ rta2 ∆, rta2 ∆/ rta2 ∆:: P ADH1 - CDR1 , cdr1 ∆/ cdr1 ∆) to FLC were tested by the broth microdilution assays in a YPD medium incubated at 30°C for 48 h (Left). Cells from the broth microdilution assays were spotted onto YPD medium and incubated at 30°C for 48 h before the plate was photographed (Right). (B) Disk diffusion assays showed that the loss of the CMP1 gene, but not the CDR1 gene, cleared the inhibition zones of 25 μg FLC. In brief, cells (2 × 10 5 cells) were spread onto YPD plates. A single 25 μg FLC disk (6 mm, Liofilchem, Italy) was placed in the center of each plate. Plates were then incubated at 30 C for 48 h before plates were photographed. (C) The MIC values of FLC of the SN152 strain and the P ADH1 - CDR1 mutant in a YPD medium without or with 1 μg/ml cyclosporin A were tested by the broth microdilution assays (at 30°C for 48 h) (Left). Cells from the broth microdilution assays were spotted onto YPD medium and incubated at 30°C for 48 h before the plate was photographed (Right). (D) The MIC values of FLC of the SN152 strain and the cmp1 Δ/ cmp1 Δ null mutant in a YPD medium without or with 10 μg/ml fluphenazine (FNZ) were tested by the broth microdilution assays (at 30°C for 48 h) (Left). Cells from the broth microdilution assays were spotted onto YPD medium and incubated at 30°C for 48 h before the plate was photographed (Right). (E) The MIC values of FLC of the SN152 strain in a YPD medium with 1 μg/ml cyclosporin A, 10 μg/ml FNZ, 1 μg/ml cyclosporin A+10 μg/ml FNZ or without any compound (control) were tested by the broth microdilution assays (at 30°C for 48 h) (Left). Cells from the broth microdilution assays were spotted onto YPD medium and incubated at 30°C for 48 h before the plate was photographed (Right).

Article Snippet: Drug stock solutions were prepared using dimethyl sulfoxide (DMSO) (Sangon Biotech, Shanghai, China) as a solvent for brefeldin A (6.4 mg/ml) (MCE, Shanghai, China), cerulenin (6.4 mg/ml) (MCE, Shanghai, China), cyclosporin A (6.4 mg/ml) (Aladdin, Shanghai, China), FLC (6.4 mg/ml) (Aladdin, Shanghai, China), FNZ (6.4 mg/ml) (MCE, Shanghai, China), geldanamycin (Sangon Biotech, Shanghai, China), menadione (Aladdin, Shanghai, China), myriocin (6.4 mg/ml) (MCE, Shanghai, China), rapamycin (6.4 mg/ml) (MCE, Shanghai, China), staurosporine (6.4 mg/ml) (MCE, Shanghai, China), tacrolimus (6.4 mg/ml) (Aladdin, Shanghai, China), and terbinafine (6.4 mg/ml) (MCE, Shanghai, China).

Techniques: Incubation, Diffusion-based Assay, Inhibition, Mutagenesis, Control

Journal: Frontiers in Pharmacology

Article Title: Myriocin enhances the antifungal activity of fluconazole by blocking the membrane localization of the efflux pump Cdr1

doi: 10.3389/fphar.2022.1101553

Figure Lengend Snippet: The synergistic antifungal activity of FLC and some compounds. Dose-matrix titration assays showed that some compounds (concentration range from 0.25 to 16 μg/ml) enhanced the antifungal activity of FLC in the presence of FNZ (10 μg/ml) (The MIC values of FLC reduced from 4 to 1 μg/ml or lower).

Article Snippet: Drug stock solutions were prepared using dimethyl sulfoxide (DMSO) (Sangon Biotech, Shanghai, China) as a solvent for brefeldin A (6.4 mg/ml) (MCE, Shanghai, China), cerulenin (6.4 mg/ml) (MCE, Shanghai, China), cyclosporin A (6.4 mg/ml) (Aladdin, Shanghai, China), FLC (6.4 mg/ml) (Aladdin, Shanghai, China), FNZ (6.4 mg/ml) (MCE, Shanghai, China), geldanamycin (Sangon Biotech, Shanghai, China), menadione (Aladdin, Shanghai, China), myriocin (6.4 mg/ml) (MCE, Shanghai, China), rapamycin (6.4 mg/ml) (MCE, Shanghai, China), staurosporine (6.4 mg/ml) (MCE, Shanghai, China), tacrolimus (6.4 mg/ml) (Aladdin, Shanghai, China), and terbinafine (6.4 mg/ml) (MCE, Shanghai, China).

Techniques: Activity Assay, Titration, Concentration Assay

Journal: Frontiers in Pharmacology

Article Title: Myriocin enhances the antifungal activity of fluconazole by blocking the membrane localization of the efflux pump Cdr1

doi: 10.3389/fphar.2022.1101553

Figure Lengend Snippet: Myriocin can significantly reduce theMIC values of FLC against (A) C. albicans isolates ( n = 38) (** p = 0.0017, the FNZ (10 μg/ml) + myriocin (0.5 μg/ml) treated group compared to the FNZ (10 μg/ml) group, t-Test) and (B) C. auris isolates ( n = 5) (* p = 0.036, the FNZ (10 μg/ml) + myriocin (0.5 μg/ml) treated group compared to the FNZ (10 μg/ml) group, t-Test).

Article Snippet: Drug stock solutions were prepared using dimethyl sulfoxide (DMSO) (Sangon Biotech, Shanghai, China) as a solvent for brefeldin A (6.4 mg/ml) (MCE, Shanghai, China), cerulenin (6.4 mg/ml) (MCE, Shanghai, China), cyclosporin A (6.4 mg/ml) (Aladdin, Shanghai, China), FLC (6.4 mg/ml) (Aladdin, Shanghai, China), FNZ (6.4 mg/ml) (MCE, Shanghai, China), geldanamycin (Sangon Biotech, Shanghai, China), menadione (Aladdin, Shanghai, China), myriocin (6.4 mg/ml) (MCE, Shanghai, China), rapamycin (6.4 mg/ml) (MCE, Shanghai, China), staurosporine (6.4 mg/ml) (MCE, Shanghai, China), tacrolimus (6.4 mg/ml) (Aladdin, Shanghai, China), and terbinafine (6.4 mg/ml) (MCE, Shanghai, China).

Techniques: