Table 1.
In vitro toxicity characteristics and drug-like properties of DHCA and Mal-gluc
| Toxicity and drug-like property assays | Malvidin-gluc | DHCA | |
|---|---|---|---|
| In vitro assays for toxicity | MTT assay | ||
| % of vehicle control | 100% | 100% | |
| LDH assay | |||
| % of vehicle control | 100% | 100% | |
| Cytotoxicity by high content screening (AC50) | |||
| Cell number | 176 µM ↓ | NR | |
| Nuclear size | 88.4 µM ↑ | NR | |
| DNA structure | NR | NR | |
| Cell membrane permeability | 52.7 µM ↓ | 56.6 µM ↓ | |
| Mitochondrial mass | 176 µM ↑ | NR | |
| Mitochondrial membrane potential | NR | >200 µM ↑ (NS) | |
| Cytochrome C release | NR | >200 µM ↑ | |
| Cardiotoxicity (IC50) | |||
| hERG inhibition | >25 µM | >25 µM | |
| In vitro assays for drug-like properties | CPY450 inhibition (IC50) | ||
| CYP2D6 | >25 µM | >25 µM | |
| CYP3A4 | >25 µM | >25 µM | |
| CYP1A2 | >25 µM | >25 µM | |
| CYP2C9 | >25 µM | >25 µM | |
| CYP2C19 | >25 µM | >25 µM | |
| CYP2C8 | >25 µM | >25 µM | |
| CYP2B6 | >25 µM | >25 µM | |
| Plasma stability | |||
| Half-life (mouse plasma) | 201 min | 44.1 min | |
| Half-life (human plasma) | 250 min | 66.7 min | |
| Brain homogenate stability | |||
| Half-life (mouse homogenate) | 29.4 min | 16.1 min | |
| Plasma protein binding | |||
| Mean fraction unbound (mouse plasma) | 55.70% | N/A | |
NR, No response observed; N/A, Not performed due to the short half-life in plasma; AC50, The concentration at which 50% maximum effect is observed for each cell health parameter; IC50, The concentration at which 50% maximum inhibition is observed for each parameter; ↓↑, Decrease or increase of response; NS, Fit not statistically significant