Table II.
Effect of two 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 (caffeine) | 0.6 | ++ | >2 |
| 30 | 1-CH2CH3 | 3-CH2CH3 | Inactive | ++ | 2 |
| 31 | 1-CH2C≡CH | 3-H | Inactive | ++ | >2 |
| 32 | 1-H | 3-H | Inactive | + | >2 |
| 33 | 1-CH2CH=CH2 | 3-CH2CH=CH2 | Inactive | ++ | >2 |
| 34 | 1-CH2C≡CH | 7-CH2C≡CH | Inactive | − | 1 |
| 35 | 1-CH2CH2CH3 | 8-phenyl | Inactive | − | 0.2 |
| 36 | 1-CH2CH2CH3 | 8-cyclopentyl | Inactive | + | 0.2 |
| 37 | 3-CH2CH(CH3)2 | 7-H (IBMX) | Inactive | ++ | 1 |
| 38 | 3-CH2CH(CH3)2 | 7-CH2C≡CH | Inactive | ++ | 2 |
| 39 | 3-CH2CH2CH3 | 7-CH2CH2CH3 | Inactive | ++ | 1 |
| 40 | 3-CH2C≡CH | 7-CH2C≡CH | Inactive | + | 2 |
| 41 | 3-H | 7-H | Inactive | + | >2 |
| 42 | 3-CH2CHCH3 | 7-H | Inactive | ++ | >2 |
| 43 | 7-H | 8-CF3 | Inactive | − | >2 |
| 44 | 7-H | 8-cyclopentyl | 0.6 | − | 2 |
| 45 | 7-H | 9-CH3 (isocaffeine) | Inactive | ++ | >2 |
a
Concentration required to achieve 50% of the maximal G2 checkpoint inhibition elicited by caffeine.
b
++, no precipitates observed at all on 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.