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.