Relationship between biological activity and dipole moment in benzo[a]phenothiazines

Relationship between the biological activity and two different dipole moments were investigated in 9 benzo[a]phenothiazines [1-8] by calculating the dipole moment with the PM3 method. 12H-Benzo[a]phenothiazine [1], 9-methyl-12H-benzo[a]phenothiazine [2], 10-methyl-12H-benzo[a]phenothiazine[3] and 11-methyl-12H-benzo[a]phenothiazine [4] induced monocytic differentiation of human myelogenous leukemic cell lines and displayed antitumor activity. These active compounds showed a significantly smaller value of calculated ground-state dipole moment (mu g) and larger value of first excited-state dipole moment (mu e). The mu e/mu g ratio of four active compounds [1-4] ranged from 3.25 to 4.38, whereas that of three inactive compounds [5,6,7] ranged from 1.77 to 2.72. These two different dipole moments might be useful parameters for estimation of the biological activity of benzo[a]phenothiazines [1-8].