Schistosomiasis hycanthone

Intercalation has been demonstrated with a number of other compounds having a polycyclic aromatic system and groups capable of forming hydrogen bonds. Among such compounds are the antibacterial 9-aminoacridine, the antimalarials mepacrine and chloroquine, the veterinary trypanocide ethidium (246), the thioxanthone lucanthone (247 R = Me) and its more active metabolite hycanthone (247 R = CH20H), which are used in the treatment of schistosomiasis, and the antineoplastic alkaloid ellipticine (248). A number of antibiotics, including the actinomycins, echinomycin and bleomycin, also intercalate. 

Predecessors to praziquantel as the preferred treatment for schistosomiasis include oxamniquine, and the related compound hycanthone (Cioli et al., 1995). These drugs act by inhibiting nucleic acid synthesis, but only after parasite-mediated biotransformation of the drug by a schistosome enzyme (Cioli et al., 1993, 1985). Until relatively recently, oxamniquine continued to be the primary drug used to treat schistosomiasis in Brazil. 

Dias, L.C., Pedro, R.J. and Debelardini, E.R. (1982) Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone resistance of Schistosoma mansoni to schistosomicidal agents. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 652-659. 

Cuimaraes, R.X., Tchakerian, A., Dias, L.C., de Almeida, F.M., Vilela, M.P., Cabeca, M. and Takeda, A.K. (1979) Resistance to hycanthone and oxamniquine in patients with a clinical hepato-intestinal form of schistosomiasis. AMB Revista da Associaco Medica Brasileira 25, 48-50. 

Katz, N. (1 975) Clinical evaluation of niridazole and hycanthone in schistosomiasis mansoni endemic areas. Journal of Toxicology and Environmental Health 1, 203-209. 

Hycanthone is a derivative of lucanthone, but has less gastrointestinal and nervous system toxicity. It is effective against both Schistosoma hematobium and Schistosoma mansoni and is given as a single intramuscular injection in doses of 1.0-2.5 mg/kg (1,2). However, it has largely been superseded in the treatment of schistosomiasis by more recent, less toxic compounds. The most common adverse reactions to hycanthone, which occur in up to... 

Hepatotoxicity occurs with hycanthone serum transaminases are often raised and less commonly there is overt jaundice (5,6). Hepatitis was the major complication with hycanthone in the treatment of schistosomiasis, sometimes associated with pancreatitis (7,8). Hycanthone has also been evaluated as a potential antitumor agent, being used as a radiosensitizer here too, hepatitis was a dose-Umiting effect, occurring in some patients with doses of 100 mg/m2 per day (3). The lowest dosage that caused hepatitis was 70 mg/m2/day. In several cases the hepatotoxicity proved fatal (SED-11, 597) (7-9). 

Oostburg BF. Clinical trial with hycanthone in schistosomiasis mansoni in Surinam. Trop Geogr Med 1972 24(2) 148-51. 

Farid Z, Smith JH, Bassily S, Sparks HA. Hepatotoxicity after treatment of schistosomiasis with hycanthone. BMJ 1972 2(805) 88-9. 

Botros SS. Effect of praziquantel versus hycanthone on deoxyribonucleic acid content of hepatocytes in murine schistosomiasis mansoni. Pharmacol Res 1990 22(2) 219-29. 

Diphenylamine (8) is readily converted into phenothiazine (111), an inexpensive product useful in the treatment of human schistosomiasis (caused by blood and liver flukes), already discussed under animal health products. The salicylanilide oxyclozonide (142) came to prominence in the 1970s. Another schistosomal agent is the metabolite of lucan-thone (143a), namely hycanthone (143b). 

Schistosomiasis S. mansoni, S. japoni-cum, S. haematobium, S. intercalatum Hycanthone, niridazole, oxam-niquine, emetine, dehydroemetine, praziquantel... 

The story of the development of oxamniquine started from the work of Kikuth et al. [2] who introduced lucanthone (miracil D, la), a thioxanthone derivative, in the chemotherapy of schistosomiasis in 1946. In the biophase, the 4-methyl group of lucanthone is converted into the corresponding 4-hydroxymethyl derivative. This led Rosi, Berberian and their colleagues working at Sterling Winthrop to develop hycanthone (lb) as a better human schistosomicide than lucanthone [3-6],... 

Metrifonate (6.28), an organic phosphate much used in treating schistosomiasis, is a pro-drug from which dichlorvos (13.29) is liberated as the active form (Section 6.3.3). Lucanthone (3.42a), introduced in the 1940s for the treatment of schistosomiasis, is without effect on the worms, in vitro. This led to its replacement by hycanthone (3.42b), the true drug formed by metabolic hydroxylation (see Section 4.0, p. 141). 

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