Table 1.
Biofilm inhibitory activity of compound 9029936 against C. albicans clinical isolates and gain-of-function strains.
| Strain/Isolate | Description | Overexpressed genes | IC50 (biofilm inhibition) in μM |
|---|---|---|---|
| SC5314 | Wild-type laboratory strain | N/A | 1.875 |
| CLINICAL ISOLATES FROM AIDS PATIENT (DEVELOPED RESISTANCE OVER 2 YEARS OF FLUCONAZOLE TREATMENT) | |||
| TW1 | Clinical isolate (matched susceptible isolate for this series) | N/A | 0.8022 |
| TW2 | Clinical isolate (drug resistance observed) | MDR1 | 0.6031 |
| TW3 | Clinical isolate (drug resistance observed) | MDR1 | 2.638 |
| TW17 | Clinical isolate (multi drug resistance observed) Point mutation: R467K |
CDR1, MDR1, ERG11 | 2.767 |
| GAIN-OF-FUNCTION STRAINS OVEREXPRESSING REGULATORS OF AZOLE RESISTANCE | |||
| SCR (GOF Control) | Wild-type strain background used to generate gain-of-function strains | N/A | 1.814 |
| ScUPC2R14A | Strain with homozygous activating mutation in UPC2 (G648D) (UPC2G648D–FRT/UPC2G648D–FRT | UPC2 and ERG11 | 1.569 |
| ScMRR1R34A | Strain with homozygous activating mutation in MRR1 (P683S) (MRR1P683S–FRT/MRR1P683S–FRT | MRR1 and MDR1 | 5.494 |
| ScTAC1R34A | Strain with homozygous activating mutation in TAC1 (6980E) (TAC16980E–FRT/TAC16980E–FRT | TAC1, CDR1 and CDR2 | 4.400 |
| FLUCONAZOLE RESISTANT CLINICAL ISOLATES | |||
| 4639 | F449S, T229A (Erg11p substitutions) | MDR1, CDR1 | 1.424 |
| 4617 | F449S, T229A (Erg11p substitutions) | N/A | 0.9198 |
| 6482 | D116E, K128T, Y132H, D278N, G464S, P230L (Erg11p substitutions) |
N/A | 3.011 |
| 2440 | V437I (Erg11p substitution) | MDR1, ERG11 | 5.645 |
| 3731 | F126L, K143R (Erg11p substitutions) | MDR1 | 5.069 |
| 412 | K128T (Erg11p substitution) | N/A | 1.474 |
The IC50 values were determined from dose-response experiments looking at the ability of the compound to inhibit biofilm formation by the different C. albicans strains.