Chapter 29 : Coumarin Antibiotics: Novobiocin, Coumermycin, and Clorobiocin

Abstract:

This chapter provides an overview about coumarin antibiotics such as novobiocin, coumermycin, and clorobiocin. Novobiocin was the first antibacterial agent of this chemical class to be described. Two other chemical entities have been described in this chapter: the coumermycin complex and clorobiocin. Clorobiocin is composed of an 8-amino chlorocoumarin nucleus, a sugar (L-noviose substituted with a 5-methyl-1H-pyrrole-2-carboxylic moiety), and a benzoic chain identical to that of novobiocin. Two products are identical to coumermycin A1 (sugordomycin D-1a and sugordomycin D-1d). BL-C43 is active against gram-positive cocci and bacilli and against certain fastidious gram-negative bacilli, such as Haemophilus influenzae, Moraxella catarrhalis, Pasteurella multocida, and gram-negative cocci such as Neisseria gonorrhoeae. It is inactive against Enterobacteriaceae and nonfermentative gram-negative bacilli. This molecule appears to be slightly less active in vitro than novobiocin, but it is more active than lincomycin or erythromycin A. The determination of susceptibility by the antibiotic sensitivity test method involves disks with a dose of 5 µg. Antibacterial activities of natural coumarinic acid derivatives are listed in this chapter. Novobiocin binds to the 24-kDa protein fragment and stabilizes the structure so as to prevent the binding of triphosphate nucleosides. This reduces the pool of available enzymes and inhibits the hydrolysis of ATP. Novobiocin is well absorbed by the gastrointestinal tract. Less than 3% of the administered dose is eliminated in the urine; the drug is mainly eliminated in the bile. Concentrations in the feces are high.