Synthesis and biological activity of N-acylphenothiazines

Previous studies have demonstrated the relationship between radical intensi ty 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 cel l lines than phenothiazine, the parent compound. Electron spin resonance (E SR) spectroscopy showed that these active compounds produced much lower amo unts of radicals than phenothiazine. Several compounds failed to inhibit th e 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. (C) 2000 Elsevier Science B.V. and International Societ y of Chemotherapy. All rights reserved.