Spin-labeled rifamycin: biological activity.
3-[(2,2,6,6-Tetramethylpiperidine-4-ylimino)methyl]rifamycin (4) and spin-labeled rifamycin-3-[(2,2,6,6- tetramethyl-1-oxyl-piperidine-4-ylimino)methyl]rifamycin (1) were prepared. The structures of these compounds were determined by IR, UV, MS and 1H NMR of 4. The ESR-spectrum of 1 is a symmetric triplet signal, characteristic of nitroxyl radicals, g = 2.0025. An in vitro comparative study of the cytotoxicity and antitumor activity of 1, 4 and the initial 3-formyl-rifamycin was carried out in concentrations from 0.1 to 0.001 mM on cells before and after oxidative stress (preliminary irradiation 7Gy) on MH3924A-hepatoma rat cells, 293 transformed human fibroblasts, NBK transformed human fibroblasts and HT 1080 human fibrosarcoma. The compounds showed a cytostatic effect to 85%, with 1 being less toxic in the hepatoma cell line. In human melanoma cell lines 1 showed a higher toxicity than 4. All the derivatives (1 and 4) have in vitro antibacterial activity comparable with that of rifampicin.
Raykov
Z Z
ZZ
German Cancer Research Center, Heidelberg, Germany.
Vassilev
K
K
Grigorova
G
G
Lyapova
A
A
Alexiev
A
A
Petrov
G
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005720:Gamma Rays; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D012294:Rifamycins / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013113:Spin Labels / Q000138:chemical synthesis; D013778:Tetrazolium Salts; D013844:Thiazoles
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D012294:Rifamycins; D013113:Spin Labels; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue