Cytotoxicity and differentiation-inducing activity of phenothiazine and benzo[a]phenothiazine derivatives.
The effects of 13 phenothiazines, and 8 benzo[a]phenothiazines on the growth and differentiation of various human cultured cell lines were investigated. Perphenazine dimaleate and chlorpromazine hydrochloride were more cytotoxic against human normal fibroblasts and glioma cells than 19 other related compounds. The differentiation of three human myelogenous leukemic cell lines (ML-1, U-937, THP-1) into maturing monocytes/macrophages was potently induced by 12H- benzo[a]phenothiazine and 5-oxo-5H-benzo[a]phenothiazine. The differentiation--inducing activity of phenothiazine, and other benzo[a]phenothiazine derivatives was much less, and that of phenothiazine derivatives without the benzyl group was undetectable. Simultaneous treatment with 12H- benzo[a]phenothiazine and tumor necrosis factor produced additive, but not synergistic differentiation--induction of these cells.
Motohashi
N
N
Department of Medicinal Chemistry, Meiji College of Pharmacy, Tokyo, Japan.
Sakagami
H
H
Kamata
K
K
Yamamoto
Y
Y
D002454:Cell Differentiation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D009000:Monocytes / Q000473:pathology; D010640:Phenothiazines / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D010640:Phenothiazines