Part I: Phosphorus analogs of arylsulfonylhydrazones, Part II: Aldophosphamide substrate-like inhibitors

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dc.contributor.advisorCates, Lindley A.
dc.contributor.committeeMemberAlam, Maktoob
dc.contributor.committeeMemberMartin, Gary E.
dc.contributor.committeeMemberDyckes, Douglas F.
dc.creatorGood, Daniel James
dc.date.accessioned2022-12-20T17:29:24Z
dc.date.available2022-12-20T17:29:24Z
dc.date.issued1978
dc.description.abstractA new class of anticancer agents, arylsulfonylhydrazones of 2-formyl pyridine N-oxide, has previously been reported. Trace metal chelation by these hydrazones had been proposed as the mode of action in their antitumor activity. Four new phosphorus analogs of these hydrazones, two of which were cupric chelates, were synthesized and tested against Ehrlich carcinoma Sarcoma 180, and P388 lymphocytic leukemia. Additionally, the concurrent administration of these compounds with a solution of cupric chloride was investigated to determine the possibility of a potentiating effect of cupric chloride. A chelation study of these phosphorus analogs was also undertaken. [...] A key metabolite in the activation pathway of cyclophosphamide, a potent oncolytic agent, has been identified to be aldophosphamide [2-formyl ethyl-N,N-bis-(2-chloroethyl)phosphorodiamidate]. Through hepatic enzymatic action, aldophosphamide is rendered inactive by being oxidized to carboxyphosphamide, a non-cytotoxic metabolite. To act as potential substrates for the enzymes responsible for the degradation of aldophosphamide, several structural modifications of the basic nucleus were attempted. One potential substrate-like inhibitor was isolated as a 2,4-dinitrophenyl hydrazone. The precursor to this potential inhibitor was also isolated.
dc.description.departmentPharmacy, College of
dc.format.digitalOriginreformatted digital
dc.format.mimetypeapplication/pdf
dc.identifier.other4237807
dc.identifier.urihttps://hdl.handle.net/10657/12983
dc.language.isoen
dc.rightsThis item is protected by copyright but is made available here under a claim of fair use (17 U.S.C. Section 107) for non-profit research and educational purposes. Users of this work assume the responsibility for determining copyright status prior to reusing, publishing, or reproducing this item for purposes other than what is allowed by fair use or other copyright exemptions. Any reuse of this item in excess of fair use or other copyright exemptions requires express permission of the copyright holder.
dc.titlePart I: Phosphorus analogs of arylsulfonylhydrazones, Part II: Aldophosphamide substrate-like inhibitors
dc.type.dcmiText
dc.type.genreThesis
thesis.degree.collegeCollege of Pharmacy
thesis.degree.departmentPharmacy, College of
thesis.degree.disciplinePharmacy
thesis.degree.grantorUniversity of Houston
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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