Antileprotic Activity

Since the causative organism of leprosy, one of the world s six major diseases, Mycobacterium leprae, is closely related to Mycobacterium tuberculosis, thio-semicarbazones have also been used as second-line drugs in the chemotherapy of leprosy [38]. The most widely used in leprosy treatment has been thiacetazone, and structure-activity relationships for it are similar to those observed for antitubercular thiosemicarbazones [39, 40]. 

Recent studies have been directed towards the synthesis of heterocyclic hydrazones which have lower toxicities than thiosemicarbazones [44], It has been proposed that the hydrazinic N-H group is essential for activity since it might be involved in a crucial radical formation step important in the mechanism of RDR. This is supported by the loss of antileprotic activity for this series of compounds when the hydrazinic hydrogen is replaced by a methyl group [44]. The heterocyclic hydrazones, like thiosemicarbazones, behave as tridentate ligands. 

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Although the precise mechanism of the antileprotic activity of clofazimine has yet to be determined several explanations have been proposed (Hooper 1987). 

Acedapsone (127), which is conveniently prepared by acetylation of dapsone, was intended to be a prodrug. Leprous patients being treated with dapsone were observed to have a lower incidence of malaria and acedapsone was made to capitalize on this observation. It, indeed, has both antileprotic and antimalarial activity. 

It may also have ANTIPSYCHOTIC activity, dapiprazole hydrochloride dapiprazole. dapitant [inn] (RPR 100893) is a substituted isoindole, a TACHYKININ RECEPTOR ANTAGONIST, selective for the NK,-receptor subtype. It has potential as an ANTIMIGRAINE AGENT, dapsone [ban, inn, usan] is a sulphone with actions similar to SULPHONAMIDES and with ANTIBACTERIAL activity. It can be used as an antileprotic and for infective dermatitis herpetiformis. and is being investigated for the treatment and prevention of Pneumocystis carinii pneumonia (e.g. in AIDS), daptomycin [ban, inn, usan] is an (aminoglycoside) antibiotic. It has antibacterial properties. 

Clofazimine is active against Mycobacterium leprae and is used clinically to treat leprosy (Hansen s disease). It was s)mthesised in 1957 by Barry et al.. Laboratories of the Medical Research Council of Ireland, Trinity College Dublin. The precise mechanism of the antileprotic action of clofazimine has not been established. The World Health Organisation classify clofazimine as an "essential drug" and recommend its use, in combination, with other agents to treat all cases of leprosy (WHO, 1982). 

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