Relationship between pi-electron distribution and anticancer activity of benzo[a]phenothiazines.
In order to study the correlation between the anti-tumor activity of benzo[a]phenothiazines and the electron densities, the Huckel orbital method and modified-neglect-of-diatomic overlap (MNDO) orbital method were used. 9-Methyl-12H-benzo[a]phenothiazine (2), which showed the most potent anticancer activity among benzo[a]phenothiazines, had the highest charge of nitrogen atom (QN), L-region (QL) and M-region (QM) in the molecule. The other derivatives, which showed weaker anticancer activity, had a much reduced value of these charges (QN, QL, QM). The data suggest that stability of pi-electron in 1 benzene ring and 1 naphthalene ring in the benzo[a]phenothiazine skeleton might be responsible for the induction of anticancer activity.
Motohashi
N
N
Department of Medicinal Chemistry, Meiji College of Pharmacy, Tokyo, Japan.
Sasaki
Y
Y
Wakabayashi
Y
Y
Sakagami
H
H
Molnar
J
J
Kurihara
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D015394:Molecular Structure; D010640:Phenothiazines / Q000737:chemistry* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D010640:Phenothiazines