Novenamine is the active moiety in novobiocin

• Published in: Journal of antibiotics 1986-02, Vol.39 (2), p.272-274
• Main Authors: REUSSER, F, DOLAK, L. A
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; DNA Replication - drug effects; Escherichia coli - drug effects; Medical sciences; Novobiocin - analogs & derivatives; Novobiocin - pharmacology; Pharmacology. Drug treatments; Structure-Activity Relationship; Topoisomerase II Inhibitors
• ISSN: 0021-8820; 1881-1469

Novobiocin inhibits semiconservative DNA replication in procaryotes and more specifically DNA gyrase, an enzyme essential for DNA replication. Chemically, novobiocin consists of three distinct entities: the sugar noviose, a coumarin residue and a benzoic acid derivative. The subentity consisting of noviose plus the coumarin residue is referred to as novenamine; the subentity consisting of the coumarin plus the benzoic acid derivative is referred to as novobiocic acid. These subentities as well as noviose and the benzoic acid residue are essentially devoid of inhibitory activity against whole bacterial cells. These fragments were tested for their ability to inhibit DNA replication in a permeabilized Escherichia coli cell system and as potential inhibitors of DNA gyrase. Of all the fragments tested, only novenamine was found to inhibit DNA replication and DNA gyrase. The potency of novenamine essentially equaled that of novobiocin. This subunit thus represents the minimal structural entity necessary to interact with DNA gyrase.