Relationship between cytotoxic activity and dipole moment for phthalimido- and chloroethyl-phenothiazines.
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.
Kurihara
T
T
Faculty of Science, Josai University, Saitama, Japan. Tkuri@josai.ac.jp
Motohashi
N
N
Sakagami
H
H
Molnár
J
J
D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D004583:Electrons; D018922:HL-60 Cells; D006801:Humans; D015233:Models, Statistical; D010640:Phenothiazines / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
D010640:Phenothiazines