title: Relationship between cytotoxic activity and dipole moment for phthalimido- and chloroethyl-phenothiazines.
abstract: 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.
authors.affiliation: Faculty of Science, Josai University, Saitama, Japan. Tkuri@josai.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kurihara
authors.forename: N
authors.initials: N
authors.lastname: Motohashi
authors.forename: H
authors.initials: H
authors.lastname: Sakagami
authors.forename: J
authors.initials: J
authors.lastname: Molnár
mesh_terms: 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
chemical_list: D010640:Phenothiazines