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  • Title: Action of a new floxacrine derivative (S 82 5455) on asexual stages of Plasmodium berghei: a light and electron microscopical study.
    Author: Raether W, Mehlhorn H.
    Journal: Zentralbl Bakteriol Mikrobiol Hyg A; 1984 Mar; 256(3):335-41. PubMed ID: 6375212.
    Abstract:
    The floxacrine derivative S 82 5455, 7-chloro-1-( 4N - methylpiperazino -1N-imino)-10-hydroxy-1, 2, 3, 4-tetrahydro-3-(4-trifluoromethylphenyl)-9(10 H)- acridone , shows a high activity against blood induced infection of a drug-sensitive line of Plasmodium berghei in mice and rats. The dosis curativa minima/ dosis tolerata maxima values against the drug-sensitive P. berghei strain ascertained in the '28-day test' in mice, were 1.56 (X 5)/400 (X 1) mg/kg after the oral route 3.12(X 5)/400(X 1) mg/kg after the subcutaneous (sc) route. Morphological changes in erythrocytic stages of P. berghei following a single oral/sc dose of 25 and 50 mg/kg respectively in rats were at first swollen lacunes of the endoplasmic reticulum and extremely enlarged mitochondrion (6 h after treatment), then an apparent vacuolisation of the cytoplasm and pyknosis of the nucleus, as well as distinctly enlarged perinuclear space and later marked fissuring of the cytoplasm. After 23 h most of the parasites were destroyed by disruption of their pellicle. The majority of the degenerate parasites were situated outside of the apparently ruptured host cell. The remnants of damaged parasites and host cells disappeared completely from smears 96 h after treatment at all oral and sc doses used.
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