David Rosi

SCHISTOSOMICIDAL ACTIVITY OF LUCANTHONE HYDROCHLORIDE, HYCANTHONE AND THEIR METABOLITES IN MICE AND HAMSTERS

The schistosomicidal activities of hycanthone, the hydroxymethyl analog and the most active metabolite of lucanthone, and several human liver microsomal conversion metabolites of both compounds were tested against experimentally induced S. mansoni infection in mice and hamsters. The compounds were administered intragastrically (twice daily for 5 days) to groups of infected animals. Lucanthone, hycanthone, and two of the salts of hycanthone were also administered parenterally (single dose medica- tion). Hycanthone was the most active metabolite of lucanthone. On an equal weight basis the schis- tosomicidal activity of intragastrically administered hycanthone was 9 times greater in hamsters and 3 times greater in mice than that of lucanthone. Desethyl analogs and the sulfoxides of both compounds were less active than either parent compound. When administered parenterally lucanthone was inac- tive whereas hycanthone was highly schistosomicidal. The activity of a single dose of hycanthone ad- ministered parenterally was equal to that obtained by a 5-day regimen administered intragastrically, and the activity was maximal when given intravenously. It is generally conceded that the schisto- somicidal activity of thioxanthones depends upon the presence of the methyl group at the 4-position para to an amino side chain at the 1-position of Ring C. Alterations of the basic side chain cause changes in activity but re- placement of the 4-methyl group results in complete loss of activity (Mauss, Koelling, and