Aminocoumarin

Aminocoumarin is a class of

• Novobiocin, Albamycin (Pharmacia And Upjohn)
• Coumermycin
• Clorobiocin

Structure

The core of aminocoumarin antibiotics is made up of a 3-amino-4,7-dihydroxycumarin ring, which is linked, e.g., with a sugar in 7-Position and a benzoic acid derivative in 3-Position.^{[citation needed]}

Clorobiocin is a natural antibiotic isolated from several Streptomyces strains and differs from novobiocin in that the methyl group at the 8 position in the coumarin ring of novobiocin is replaced by a chlorine atom, and the carbamoyl at the 3' position of the noviose sugar is substituted by a 5-methyl-2-pyrrolylcarbonyl group.^[4]

Mechanism of action

The aminocoumarin antibiotics are known inhibitors of DNA gyrase. Antibiotics of the aminocoumarin family exert their therapeutic activity by binding tightly to the B subunit of bacterial DNA gyrase, thereby inhibiting this essential enzyme.^[5] They compete with ATP for binding to the B subunit of this enzyme and inhibit the ATP-dependent DNA supercoiling catalysed by gyrase.^[6] X-ray crystallography studies have confirmed binding at the ATP-binding site located on the gyrB subunit of DNA gyrase.^[4] Their affinity for gyrase is considerably higher than that of modern fluoroquinolones, which also target DNA gyrase but at the gyrA subunit.^[7]

Resistance

Resistance to this class of antibiotics usually results from genetic mutation in the gyrB subunit.^[8] Other mechanisms include de novo synthesis of a coumarin-resistant gyrase B subunit by the novobiocin producer S. sphaeroides .^[7]

Clinical use

The clinical use of this antibiotic class has been restricted due to the low water solubility, low activity against gram-negative bacteria,^[6] and toxicity in vivo of this class of antibiotics.^[9]

References