Relationship between cytotoxic activity and dipole moment for phthalimido- and chloroethyl-phenothiazines
Kurihara, T.; Motohashi, N.; Sakagami, H.; Molnár, J.
Anticancer Research 19(5b): 4081-4083
1999
ISSN/ISBN: 0250-7005 PMID: 10628357 Document Number: 505103
Among twelve phenothiazine-related compounds, the cytotoxic activity of six "half-mustard type" phenothiazines [7-12] was significantly higher than that of six phthalimido compounds [1-6]. 1-(2-Chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)propylurea [9], 1-(2-chloroethyl)-3-(2-chloro-10H-phenothiazin-10-yl)butylurea+ ++ [10] and 1-(2-chloroethyl)-3-(2-trifluoromethyl-10H-phenothiazin-10-yl)b utylurea [12] showed the highest cytotoxic activity, in parallel with high delta mu (difference between two dipole moments, mu g and mu e). There was also positive relationship between cytotoxic activity and molecular orbital energy such as pi-LUMO, pi-HOMO, and lone pair orbitals originated from O, N1, and N3 atoms. The present study demonstrated that cytotoxic activity of "half-mustard type" phenothiazines can be predicted by their dipole moments and molecular orbital energies.