Design And Synthesis Of 8-hydroxyquinoline Derivatives For The Diagnosis And Treatment Of Cancer | 22590
Journal of Cancer Science & Therapy
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8-Hydroxyquinoline (8HQ or oxine) and its derivatives are potent metal chelating agents and often used as fluorescence
sensors of Zn2+ and other metal cations. Recently, 8HQ have also been proposed as potential candidates for enzyme inhibitors
and drugs to treat cancer, HIV, neurodegenerative diseases, and so on. In this paper, we present (i) the design and synthesis
of 8HQ-based radioprotective agents for radiation therapy and (ii) the application of the photochemical cleavage reaction
of 8-quinolinyl sulfonates (8QS) to the isolation of intact ligand-receptor complexes or living target cells. (i) In radiation
therapy, adverse side effects are often induced due to the apoptosis that occurs in radiosensitive normal cell mainly caused
by apoptosis-induction by the p53 protein. Therefore, radioprotective drugs that can protect normal cells from radiation by
temporary inhibition of p53 functions are be highly desirable. We have screened some zinc (II) chelators for the inhibition of
radiation-induced p53-dependent apoptosis in MOLT-4 cells and found that N,N?-bis(2-pyridylmethyl)-1,2-ethanediamine
and some 8HQ derivatives have the potent radioprotective activity, accompanied by a low cytotoxicity. (ii) We previously
discovered the photochemical S-O bond cleavage reactions of 8QS in aqueous solution at neutral pH. Its application to QSbased
photocleavable biotin-linkers for the isolation and recovery of the intact ligand-receptor complexes or living cells such
as specific tumor cells will be presented.
Shin Aoki graduated from the University of Tokyo and received PhD from the same University in 1992. After working as an Assistant Professor at the University of
Tokyo, a Postdoc at the Scripps Research Institute, USA and an Assistant Professor in Hiroshima University, he became a Professor at the Faculty of Pharmaceutical
Sciences, Tokyo University of Science in 2003. He is a recipient of several awards including the Pharmaceutical Society of Japan Award for Young Scientists
(2002). His research interests include bioorganic chemistry, supramolecular chemistry, photochemistry, and medicinal chemistry.
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