The Metabolism Of Chloroquine Phosphate By Rat Liver Cell Fractions

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dc.contributor.advisorAsante, G.S.
dc.contributor.advisorToothill,C.
dc.contributor.authorYeboah, P.O.
dc.contributor.otherUniversity of Ghana, College of Health Sciences, School of Biomedical and Allied Health Sciences, Department of Medical Biochemistry
dc.date.accessioned2015-11-19T10:22:44Z
dc.date.accessioned2017-10-13T17:59:32Z
dc.date.available2015-11-19T10:22:44Z
dc.date.available2017-10-13T17:59:32Z
dc.date.issued1979-06
dc.descriptionThesis(M.Phil)-University of Ghana, 1979en_US
dc.description.abstract1. The metabolisn of chloroquine phosphate by the various subcellular fractions of the rat liver honnogenate has been studied. (a) Both the mitochondrial and soluble fractions were found to contain enzyme systems that degraded chloroquine to varying degrees. (b) The maximum activity of chloroquine degradation was however found in the microsomal fraction, 2. In vitro studies on the metabolisij of (ring-3-^C) chloroquine led to the conclusion that the microsomal subcellular fraction was capable of breaking chloroquine down to a minimum of eight metabolites in which the 4-aminoquinoline nucleus remained intact. 3. A number of 4-aminoquinoline derivatives, including the 4'-hydroxy, the 4'-aldehyde, the primary amine (SN 13617) derivatives of chloroquine have been successfully synthesized and characterized, 4. Using the synthesized derivatives of chloroquine as chromatographic standards, four of the eight metabolites of chloroquine (see ' 2 * above) were identified as the primary amine derivative (SN 13617), the 4'-hydroxy and the 4'-aldehyde derivatives and 7 -chloro-4-aminoquinoline. 5. Based on in vitro studies on the metabolism of both chloroquine and the synthesized derivatives by the hepatic microsomal fraction of rat, it has been tentatively suggested that the metabcLlic degradation of chloroquine proceeds by the formation of the following metabolit.££.• in the order: i) The hydroxychloroquine, HCQ (ie. the analogue of chloroquine in which a hydroxyl group has been substituted in the 2-position of N-ethyl groups). ii) The secondary amine derivative (SN 13616); iii) The primary amine derivative (SN 13617); iv) The 4'-aldehyde derivative, which is largely converted into the 4'-hydroxy derivative. 6 . An alternative pathway for the secondary amine derivative ('SN 13616) has also been proposed. Through this pathway, chloroquine may be converted through SN 13616 and an unidentified intermediate V, to a final product 4-amino-7-chloroquinoline. It has also been demonstrated that in presence of SKF 525A, the metabolism of chloroquine is apparently activated through the latter alternative pathway. 7. Evidence is also presented to show that the proposed pathway for chloroquine metabolism might be common to both the rat and man.en_US
dc.format.extentxiv, 143p.
dc.identifier.urihttp://197.255.68.203/handle/123456789/7179
dc.language.isoenen_US
dc.publisherUniversity of Ghanaen_US
dc.rights.holderUniversity of Ghana
dc.titleThe Metabolism Of Chloroquine Phosphate By Rat Liver Cell Fractionsen_US
dc.typeThesisen_US

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