Toxic and inflammatory properties of two antibiotics: Muconomycin A and B

Abstract

Toxicological investigations were conducted on two new antibiotics, Muconomycin A and Muconomycin B. These non-nitrogenous antibiotics were found to be highly toxic and capable of inducing profound inflammation in the peritoneal cavity of male albino rats. Either antibiotic produced large volumes (10-20 ml) of inflammatory exudate even when injected intrapentoneally in quantities of 1.6 x 10-10 moles. An extensive profile of the electrolytes and proteins found in inflammatory exudates was developed. Simultaneous assays of the blood serum of treated rats provided a basis for comparing the concentrations of constituents of serum with those of the exudate. The results of these assays showed that the exudate contained lower concentrations of sodium and proteins, and greater amounts of potassium, calcium, and phosphorus than the serum. Chloride ion concentrations were variable. Since previous work showed that one of the manifestations of toxicity of these substances was the production of creatinuria, further studies were carried out with ATP/Creatine Phosphotransferase. These studies show that these antibiotics are potent in vitro inhibitors of the enzyme ATP/Creatine Phosphotransferase.Aletabolites derived from cultures of molds in the Myrothecium genus have been reported to have a wide range of biological activity. In 1946 and 1947 Brian, McGowan, et al.l-* reported that, while handling large quantities of culture fluid of Myrothecium verrucaria, they experienced severe facial inflammation, desquamation, and local irritation. In 1961 Nespiak et aL3 showed that metabolites of Myrothecium roridum were potent fungicides, and in 1962 Kishaba et aL4 *

In Silico analysis of Escherichia coli polyphosphate kinase (PPK) as a novel antimicrobial drug target and its high throughput virtual screening against PubChem library

“…The shortlisted compounds interacted intimately with the PPK molecule in the tunnel region forming hydrogen bonds and thus blocking the site of ATP attachment. Among these compounds, Muconomycin A has been found highly toxic and capable of inducing inflamation [18] and Etoposide has been reported to produce significant genotoxic effect to eukaryotes [19]. However, Dynemicin A remains a promising compound due to its low cytotoxicity [20] and high affinity to PPK active site.…”