Semisynthetic drugs rifamycins

If a drug fails to meet present day standards because of low in vitro potency, metabolic, or chemical instability, poor oral absorption or high degree of serum and tissue binding, experience teaches that the prospects for improvement via structural modification are good—if systematic structural modification with retention of biological activity is feasible. The clinically established semisynthetic cephalosporins, rifamycin SV and rifampicin represent precisely this kind of improvement, while laboratory data indicate that it has also been achieved in the coumermycin series as well (96, 97). 

Rifaximin, a virtually nonabsorbed antibiotic, is a semisynthetic rifamycin derivative, with a broad antimicrobial spectrum that includes most Gram-positive and Gram-negative bacteria, both aerobes and anaerobes [1, 2], Unlike systemically available antibiotics, this antimicrobial allows localized targeting (e.g. enteric or cutaneous) of pathogens and is associated with a minimal risk of systemic toxicity or side effects [3, 4], Provided that nonabsorbed antibiotics are as effective as systemically absorbed drugs for the target illness, their safety and toler-... 

The rifamycins, a class of antibacterials isolated from Streptomyces mediterranei, contain a macrocyclic ring bridging across two nonadjacent positions on an aromatic system. Rifampicin (9.96), a semisynthetic derivative of rifamycin, is a drug of choice in the treatment of tuberculosis as well as leprosy, either alone or in combination with other drugs. Rifampicin is much safer than other antituberculotics since it inhibits DNA-directed RNA polymerase in bacteria but not in mammals. Another rifamycin, rifabutin (9.97), is a spiroimidazopiperidyl derivative of the rifamycin. 

Rifampicin (Fig. 10.70) is a semisynthetic rifamycin made from rifamycin B—an antibiotic isolated from Streptomyces mediterranei. It inhibits Gram-positive bacteria and works by binding non-covalently to RNA polymerase and inhibiting RNA synthesis. The DNA-dependent RNA polymerases in eukaryotic cells are unaffected, since the drug binds to a peptide chain not present in the mammalian RNA polymerase. It is therefore highly selective. 

Antituberculin Agents. Rifampin [13292 6-1], a semisynthetic derivative of rifamycin SV, is a most valuable drug for treatment of tuberculosis, an infection caused by mycobacteria, leprosy, and an expanding range of other infections (23). Cycloserine [64-41-7] has been used to a limited extent for treatment of tuberculosis as a reserve drug. Although cycloserine inhibits bacteria by interfering with their cell wall biosynthesis, it has toxic side effects in humans in the form of neurotoxicity. Capreomycin [11003-38-6] and to a much lesser extent viomycin [32988-50-4]y both of which are peptides, have also been used for treatment of this disease. 

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