Relationship between Electronic Structure and Cytotoxic Activity of Dopamine and 3-Benzazepine Derivatives

Abstract

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 (μ_ESP-G and μ_ESP-W) and heat of formation (ΔH_f) 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 ΔΔH_f values, whereas thirteen derivatives [4-8, 10-11, 14-19] (CC₅₀: > 3.6 mM) showed the weakest cytotoxic activity with large ΔΔH_f values.