Towards a selective cytotoxic agent for prostate cancer: interaction of zinc complexes of polyhydroxybenzaldehyde thiosemicarbazones with topoisomerase I

Tan, K.W.; Seng, H.L.; Lim, F.S.; Cheah, S.C.; Ng, C.H.; Koo, K.S.; Mustafa, M.R.; Ng, S.W.; Maah, M.J. (2012) Towards a selective cytotoxic agent for prostate cancer: interaction of zinc complexes of polyhydroxybenzaldehyde thiosemicarbazones with topoisomerase I. Polyhedron, 38 (2012). pp. 275-284. ISSN 0277-5387

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    Abstract

    Four thiosemicarbazones ligands,H3T(1),H3M(2),H3E(3) andH3P(4) have been prepared with good yield by refluxing 2,4-dihydroxybenzaldehyde with N(4)-substituted thiosemicarbazide in ethanol (H3T(1) = 2,4-dihydroxybenzaldehyde thiosemicarbazone;H3M(2) = 2,4-dihydroxybenzaldehyde 4-methylthiosemicarbazone; H3E(3) = 2,4-dihydroxybenzaldehyde 4-ethylthiosemicarbazone and H3P(4) = 2,4-dihydroxybenzaldehyde 4-phenylthiosemicarbazone). Reactions of these ligands with zinc acetates in the presence of 2,20-bipyridine lead to the formation of zinc(II) complexes of formulation Zn(bpy)L(5�8) (bpy = 2,20-bipyridine; L = doubly deprotonated thiosemicarbazones = HT(5); HM(6); HE(7) and HP(8)). These compounds were characterized and their cytotoxicity and topoisomerase I inhibition activities studied. X-ray diffraction study indicates that complex 8 is five coordinated and the coordination geometry around zinc(II) is trigonal bipyramidal distorted square based pyramid (TBDSBP). The doubly deprotonated thiosemicarbazone acts as a tridentate ONS-donor ligand while 2,2-bipyridne as the NN-donor ligand. Complexes 6, 7 and 8 are more cytotoxic towards PC3 (prostate cancer cell line) than RWPE-1 (prostate normal cell line). The cytotoxicity and topoisomerase I inhibition activities seem to be dependent on the N(4) substituent of the thiosemicarbazone moiety.

    Item Type: Article
    Creators:
    1. Tan, K.W.
    2. Seng, H.L.
    3. Lim, F.S.
    4. Cheah, S.C.
    5. Ng, C.H.
    6. Koo, K.S.
    7. Mustafa, M.R.(Department of Pharmacology, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA)
    8. Ng, S.W.
    9. Maah, M.J.
    Journal or Publication Title: Polyhedron
    Additional Information: Corresponding author. E-mail address: mjamil@um.edu.my (M.J. Maah).
    Uncontrolled Keywords: Cytotoxicity, Schiff base, Topoisomerase I, Prostate cancer, Zinc, Thiosemicarbazone
    Subjects: R Medicine
    Divisions: Faculty of Medicine
    Depositing User: Ms Haslinda Lahuddin
    Date Deposited: 12 Jun 2012 12:06
    Last Modified: 12 Jun 2012 12:06
    URI: http://eprints.um.edu.my/id/eprint/3295

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