Hycanthone resistance in schistosomes correlates with the lack of an enzymatic activity which produces the covalent binding of hycanthone to parasite macromolecules

Molecular and Biochemical Parasitology
Livia Pica-MattocciaD Cioli

Abstract

Crude extracts of hycanthone sensitive Schistosoma mansoni incubated at 37 degrees C in the presence of ATP and Mg2+ induced the covalent binding of tritiated hycanthone (HC) to macromolecules. The same behavior was shown by the HC sensitive species, Schistosoma rodhaini, whereas two independently isolated HC resistant S. mansoni strains had no detectable activity. Sensitive male schistosomes had more activity than females or immature worms. Virtually no activity was present in mouse liver, in human liver, in HeLa cells or in the naturally resistant species Schistosoma japonicum. The activity was destroyed by boiling or by Proteinase K treatment. Covalent binding of tritiated HC to macromolecules could be inhibited by cold HC, oxamniquine or IA-4, while none of the in vitro ineffective analogs, like lucanthone, UK-3883 or 4-desmethyl lucanthone, were inhibitory. These results strongly support the previously advanced suggestion that HC is activated by enzymatic mechanisms which are present only in drug sensitive schistosomes.

References

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Citations

May 1, 1993·Acta Tropica·D P McManus, M Hope
Jan 1, 1995·Pharmacology & Therapeutics·D CioliS Archer
May 1, 1993·Parasitology Today·D CioliS Archer
Jun 13, 2001·International Journal for Parasitology·P Köhler
May 26, 1999·Molecular and Biochemical Parasitology·A KhattabM Q Klinkert
Apr 14, 2016·International Journal for Parasitology·Frédéric D ChevalierTimothy J C Anderson
Jul 3, 2013·FEMS Microbiology Reviews·Manu VanaerschotJean-Claude Dujardin
Feb 20, 2007·Memórias do Instituto Oswaldo Cruz·Livia Pica-MattocciaDonato Cioli
Apr 22, 2020·International Journal for Parasitology. Drugs and Drug Resistance·Anastasia R RugelPhilip T LoVerde
Jun 11, 2021·International Journal for Parasitology. Drugs and Drug Resistance·Philip T LoVerdeStanton F McHardy

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