Table 2
Structure activity relationship of ergot and dihydroergot alkaloids interactions with P-glycoprotein
| R1 | R2 | R3 | Name | Vinblastine Accumulation | Calcein-AM Accumulation | log P | CYP3A42-aKs | CYP3A42-bKi | ||
|---|---|---|---|---|---|---|---|---|---|---|
| MDR12-cKi, μM | MDR12-c | mdrIa | mdr1b | |||||||
| Ki μM | ||||||||||
| Br | CH(CH3)2 | CH2(CH3)2 | Bromocriptine | 4.0 ± 1.9 (1) | 2.81 (1) | 7.48 (1) | 6.39 (1) | 6.69 | 0.9 | 8 |
| H | CH2CH(CH3)2 | CH2(CH3)2 | α-Ergocryptine | 6.4 ± 0.5 (2) | 12.2 (2) | 43.5 (3) | 26.9 (5) | — | 1.5 | — |
| H | CH2C6H5 | CH3 | Ergotamine | 14.3 ± 4.2 (3) | 98.9 (4) | 188.8 (5) | 18.0 (3) | 4.63 | — | 12 |
| H | CH2C6H5 | CH2(CH3)2 | Ergocristine | 18.8 ± 3.0 (4) | 42.8 (3) | 39.4 (2) | 15.3 (2) | 5.56 | 1.1 | — |
| H | CH(CH3)2 | CH2(CH3)2 | Ergocornine | 24.5 ± 5.2 (5) | 105.2 (5) | 271.5 (6) | 19.1 (4) | 5.07 | — | — |
| H | Ergometrine | >100 (6) | 115.0 (6) | 117.5 (4) | 1000> (6) | 4.63 | — | — | ||
| R2 | R3 | Name | Vinblastine Accumulation | Calcein-AM Accumulation | log P | CYP3A42-aKs | CYP3A42-bKi | ||
|---|---|---|---|---|---|---|---|---|---|
| MDR12-cKi, μM | MDR12-c | mdr1a | mdr1b | ||||||
| K i μM | |||||||||
| CH2C6H5 | CH2(CH3)2 | Dihydroergocristine | 16.0 ± 5.9 (1) | 511.0 (2) | 111.5 (1) | 166.7 (2) | 5.86 | 1.6 | — |
| CH2CH(CH3)2 | CH2(CH3)2 | Dihydroergocryptine | 19.8 ± 5.4 (2) | 360.5 (1) | 333.4 (2) | 159.9 (1) | 5.90 | 0.7 | — |
| CH2C6H5 | CH3 | Dihydroergotamine | 119.9 ± 4.2 (3) | >1000 (3) | >1000 (3) | >1000 (3) | 4.94 | 0.6 | 23 |