actinobolin and bactobolin

Some derivatives of bactobolin were prepared from bactobolin (1) by transformation of the dichloromethyl group at C-3 to the hydroxymethyl, carboxylic acid, methanesulfonyloxymethyl and aldehydeoxime groups. The derivatives proved to be less active than the parent antibiotic 1 against bacteria as well as cytotoxicity, indicating that the functionality at C-3 considerably influences the biological activity.

Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Benzopyrans; Microbial Sensitivity Tests; Pyrans; Structure-Activity Relationship

3-epi-Actinobolin was synthesized by the chemical transformation of actinobolin involving a key step of the reconstruction of fused delta-lacton skeleton via intramolecular acylation reaction. The analogue with low toxicity weakly inhibits Gram-positive and Gram-negative bacteria.

Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Benzopyrans; Microbial Sensitivity Tests; Pyrans; Structure-Activity Relationship; Tumor Cells, Cultured

Some derivatives of bactobolin were prepared from bactobolin (1) by radical reduction and formation of the fused azetidine ring. The derivatives proved less active than the parent antibiotic 1 against bacteria, indicating that dichloromethyl group at C-3 position play an important role in biological activity.

Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Benzopyrans; Cell Survival; Microbial Sensitivity Tests; Molecular Conformation; Pyrans; Structure-Activity Relationship

In the search for a new drug to treat myasthenia gravis, we studied the efficacy of new immunosuppressants on experimental autoimmune myasthenia gravis (EAMG). 15-Deoxyspergualin (15-DSP), bactobolin and actinobolin were administered to some groups at the time of immunization and to other groups 10 days after. The most effective results were achieved with doses of 2.5 mg/kg daily of 15-DSP and 30 mg/kg daily of actinobolin administered from day 1. In both groups, the body weights of the rats increased as normally as those of controls and signs of myasthenia were mild. Immunoelectron microscopic examination of the neuromuscular junctions in rats treated with 2.5 mg/kg of 15-DSP appeared normal, even in the chronic phase (induced by a booster at week 4). Levels of anti-acetylcholine receptor antibodies were almost completely suppressed. Although the effects of these drugs were more remarkable when administered from day 1 than from day 10, the results suggest that they may prove useful in treating myasthenic patients.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antibody Formation; Benzopyrans; Electric Organ; Female; Guanidines; Immunosuppressive Agents; Microscopy, Immunoelectron; Myasthenia Gravis; Neuromuscular Junction; Pyrans; Rats; Receptors, Cholinergic; Torpedo

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Benzopyrans; Leukemia L1210; Mice; Protein Biosynthesis; Pyrans; Ribosomes