Pharmacochemical aspects of leprosy. Recent developments and prospects for new drugs.
From a pharmacochemical point of view the existing anti-leprotics as well as possible innovations in the chemotherapy of leprosy are discussed. Of the main anti-leprotics, which are used nowadays--dapsone, rifampicin, clofazimine, isoniazide, ethionamide and prothionamide--the mechanism of action, the main problems in their application and possibilities to develop improved variants are reviewed. Based on the chemistry of Mycobacterium leprae, the target systems for new anti-leprotics are identified. These systems include the cell wall, the catabolism of reactive oxygen species, the metabolisms of carbon sources, the amino acid metabolism and the uptake of iron. Two possible new lead structures from other fields, 4-quinolones and mycobacterial ribonucleotide reductase inhibitors are presented.
van Saane
P
P
Division of Pharmacochemistry, Free University, Amsterdam, The Netherlands.
Timmerman
H
H
D003622:Dapsone / Q000627:therapeutic use; D006801:Humans; D007917:Leprostatic Agents / Q000627:therapeutic use*; D007918:Leprosy / Q000188:drug therapy*; D009166:Mycobacterium leprae / Q000378:metabolism; D012293:Rifampin / Q000627:therapeutic use
D007917:Leprostatic Agents; D003622:Dapsone; D012293:Rifampin