Resistance of schistosomes to hycanthone and oxamniquine
Mem. Inst. Oswaldo Cruz
;
84(supl.1): 38-45, 1989. tab
Article
in English
| LILACS
| ID: lil-623564
ABSTRACT
Genetic crosses between phenotypically resistant and sensitive schistosomes demonstrated that resistance to hycanthone and oxamniquine behaves like a recessive trait, thus suggesting that resistance is due to the lack of some factor. We hypothesized that, in order to kill schistosomes, hycanthone and oxamniquine need to be converted into an active metabolite by some parasite enzyme wich, if inactive, results in drug resistance. Esterification of the drugs seemed to be the most likely event as it would lead to the production of an alkylating agent upon dissociation of the ester. An artificial ester of hycanthone was indeed active even in resistant worms, thus indirectly supporting our hypothesis. In addition, several lines of evidence demonstrated that exposure to hycanthone and oxamniquine results in alkylation of worm macromolecules. Thus, radioactive drugs formed covalent bonds with the DNA of sensitive (but not of resistant) schistosomes; an antiserum raised against hycanthone detected the presence of the drug in the purified DNA fraction of sensitive (but not of resistant) schistosomes; a drug-DNA adduct was isolated from hycanthone-treated worms and fully characterized as hycanthone-deoxyguanosine.
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Index:
LILACS (Americas)
Main subject:
Schistosoma mansoni
/
Drug Resistance
/
Hycanthone
Limits:
Animals
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
1989
Type:
Article
/
Congress and conference
Affiliation country:
Italy
/
United States
Institution/Affiliation country:
Institute of Cell Biology/IT
/
Rensselaer Polytechnic Institute/US
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