Synthesis and biological activity of N-acylphenothiazines.
Previous studies have demonstrated the relationship between radical intensity and cytotoxic activity in water-soluble compounds. This relationship was investigated in lipophilic compounds. Several N-acylphenothiazines showed higher cytotoxic activity against human leukemic and squamous carcinoma cell lines than phenothiazine, the parent compound. Electron spin resonance (ESR) spectroscopy showed that these active compounds produced much lower amounts of radicals than phenothiazine. Several compounds failed to inhibit the cytopathic effects of human immunodeficiency virus (HIV) infection in MT-4 cells. It suggested that the radical-mediated-mechanisms has not involved in the induction of cytotoxic activity by lipophilic compounds, such as N-acylphenothiazines.
Motohashi
N
N
Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo, Japan. motohasi@my-pharm.ac.jp
Kawase
M
M
Saito
S
S
Kurihara
T
T
Satoh
K
K
Nakashima
H
H
Premanathan
M
M
Arakaki
R
R
Sakagami
H
H
Molnár
J
J
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D010640:Phenothiazines / Q000138:chemical synthesis / Q000494:pharmacology*
D019380:Anti-HIV Agents; D014150:Antipsychotic Agents; D005609:Free Radicals; D010640:Phenothiazines