Table III.
Effect of multiple structural alterations of caffeine on G2 checkpoint inhibition, solubility and cytotoxicity.
| Compound number |
Structural alterations | G2 checkpoint inhibition (mM)a |
Solubilityb | Cytotoxicity IC50 (mM)c |
|||
|---|---|---|---|---|---|---|---|
| 1 | 1-CH3 | 3-CH3 | 7-CH3 (caffeine) | 0.6 | ++ | >2 | |
| 46 | 1-H | 3-CH2CH2CH3 | 7-H (enprofylline) | Inactive | ++ | >2 | |
| 47 | 1-CH2CH2CH3 | 3-H | 7-H | + | 1 | ||
| 48 | 1-CH2CH2CH3 | 3-CH2CH2CH3 | 7-H | Inactive | + | 0.5 | |
| 49 | 1-CH2CH2CH3 | 3-CH2CH2CH3 | 7-CH2CH=CH2 | Inactive | ++ | 0.5 | |
| 50 | 1-H | 3-CH2CH=CH2 | 7-CH2CH=CH2 | Inactive | + | 1 | |
| 51 | 1-CH2C≡CH | 3-CH2C≡CH | 7-CH2C≡CH | Inactive | − | 2 | |
| 52 | 1-CH2CHCH(CH3)2 | 3-CH2CH(CH3)2 | 7-H | Inactive | − | >2 | |
| 53 | 1-CH2CH2CH3 | 3-CH2CH2CH3 | 8-cyclopentyl | Inactive | − | 0.05 | |
| 54 | 1-CH2CH2CH3 | 3-CH2CH2CH3 | 8-cyclohexyl | Inactive | − | 0.2 | |
| 55 | 1-CH2CH2CH3 | 3-H | 7-H | 8-cyclopentyl | Inactive | − | >2 |
| 56 | 1-CH2CH2CH3 | 3-CH2CH2CH3 | 7-H | 8-cyclohexyl | Inactive | − | 0.02 |
| 57 | 1-CH2CH2CH3 | 3-CH2CH2CH3 | 7-H | 8-cyclopentyl | Inactive | − | 0.02 |
a
Concentration required to achieve 50% of the maximal G2 checkpoint inhibition elicited by caffeine.
b
++, no precipitates observed at all concentrations tested; +, precipitates observed at concentrations above 0.5 mM; −, precipitates observed at concentrations below 0.5 mM.
c
Determined by MTT assay as described in Materials and methods.