Radical intensity and differentiation-inducing activity of benzo[a]phenothiazines and phenothiazines.
ESR spectroscopy revealed that 12H-benzo [a]phenothiazine, 9-methyl-12H-benzo[a]phenothiazine, 10-methyl-12H-benzo [a]phenothiazine, 11-methyl-12H-benzo[a]phenothiazine and 5-axo-5H-benzo[a]phenothiazine, which induced the differentiation of human myelogenous leukemic cell lines into maturing macrophages, produced radical(s) under an alkaline condition. On the other hand, 6-hydroxy-5-axo-5H-benzo [a]phenothiazine, 6-methyl-5-oxo-5H-benzo[a]phenothiazine and 5H-benzo[a][1,4]benzothiazino-[3,2-c]phenothiazine, and 13 phenothiazines, which had little or no differentiation-inducing activity, produced no detectable amounts of radical(s). Using Hückel molecular orbital (HMO) method, these active benzo[a]phenothiazines were shown to have the elevated n-spin density at the sulfur atom of their molecules. Seven out of 8 benzo[a]phenothiazines significantly enhanced the radical intensity of sodium L-ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA), whereas only 3 out of 13 phenothiazines showed similar effects. These data suggest that the induction of human leukemic cell differentiation by benzo[a]phenothiazines might be initiated by radical mediated reactions.
Satoh
K
K
Analysis Center, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Sakagami
H
H
Kurihara
T
T
Motohashi
N
N
D002454:Cell Differentiation / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D010640:Phenothiazines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D005609:Free Radicals; D010640:Phenothiazines