7-ALKYLIDENE-SUBSTITUTED DERIVATIVES OF CEPHALOSPORINS HAVING CITOTOXIC ACTIVITY

摘要

The present invention relates to the pharmacologically active substances, particularly to cytotoxic agents for cancer chemotherapy. The mentioned compounds contain modified tert-butyl 7-methylenecephalosporanoates 1-oxide or 1,1-dioxides, in which the substituents in a 7-methylene group are specially selected from alkoxycarbonyl, alkoxycarbonyl ethylene, propinyl, aryl and heteroaryl. The majority of the compounds claimed possess cytotoxic properties against monolayer HT 1080, MG-22A, B 16 and Neuro 2A cell lines killing 50 % of cells in concentrations less than 10 mg/ml. The invented compounds are characterised by low toxicity against normal fibroblast cells and by a positive therapeutic effect in the treatment of melanoma (B 16) and sarcoma (S-180) tumor strains.