Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:5.99.1.2 (
topoisomerase
)
9,166
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Isometamidium chloride
(
ISM
) is an effective trypanocide with curative and prophylactive activity in husbandry animals. The mode of action of
ISM
against pathogenic trypanosomes is not fully understood, but there is evidence in the literature that kinetoplastic
topoisomerase
type II is selectively inhibited by the drug. This prompted the hypothesis that dyskinetoplastic trypanosomes would express a reduced level of susceptibility to
ISM
. From parental Trypanosoma evansi and T. equiperdum populations we generated clones containing only dyskinetoplastic organisms and clones containing organisms with kinetoplasts. The susceptibility of these clones to
ISM
was quantified by in vitro assays. The susceptibility of all clones was in the same range. Minor differences in drug susceptibility found between the clones showed that the dyskinetoplastic T. evansi and T. equiperdum clones were even more susceptible to
ISM
than their kinetoplastic counterparts. Thus, the hypothesis that the dyskinetoplastic trypanosomes would be less susceptible to or tolerant of
ISM
was clearly disproved. The previously demonstrated inhibition of kinetoplastic
topoisomerase
type II by
ISM
cannot be the primary toxic effect of the drug on trypanosomes, and the mode of action of
ISM
needs to be reassessed.
...
PMID:Susceptibility of dyskinetoplastic Trypanosoma evansi and T. equiperdum to isometamidium chloride. 934 50
