Screening for new antifolates of microbial origin and a new antifolate AM-8402.
A screening method was established for new specific inhibitors of folate metabolism. Culture broths of soil isolates were selected based on relative microbial activity. A culture, to be retained, must be active against Enterococcus faecium grown in a medium which contains a limited amount of pteroic acid but lacks activity against the microorganism grown in a medium supplemented with thymidine. By this screening method, three new antibiotics, diazaquinomycins A and B and AM-8402 were selected from eight thousand soil isolates. The isolation and structures of diazaquinomycins have been reported. AM-8402 is a new antifolate active against Gram-positive bacteria and mycoplasmas. It consists of a nanaomycin D moiety as chromophore and a deoxysugar and is structurally related to medermycin.
D000192:Actinomycetales / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000302:isolation & purification* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005493:Folic Acid Antagonists / Q000302:isolation & purification* / Q000494:pharmacology; D009285:Naphthoquinones / Q000302:isolation & purification* / Q000494:pharmacology; D013291:Streptococcus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D005493:Folic Acid Antagonists; D009285:Naphthoquinones; C046687:AM 8402