Relationship between electronic structure and cytotoxic activity of dopamine and 3-benzazepine derivatives.

A structure-activity relationship of dopamine and 3-benzazepine derivatives is discussed, using theoretically calculated results. In order to clearly divide dopamines and 3-benzazepines into a strongly active and a weakly active group, the CC50, two different dipole moments (microESP-G and microESP-W) and heat of formation (deltaHf) of dopamine [1-13] and 3-benzazepine derivatives [14-23] were separately calculated in two states of gas-phase and water-solution by the COSMO/PM3 method. It was found that ten derivatives [1-3, 9, 12-13 and 20-23] (CC50: 0.056 to 2.5 mM) showed the strongest cytotoxic activity with small delta(deltaHf) values, whereas thirteen derivatives [4-8, 10-11, 14-19] (CC50: > 3.6 mM) showed the weakest cytotoxic activity with large delta(deltaHf) values.