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

Tan, K.W. and Seng, H.L. and Lim, F.S. and Cheah, S.C. and Ng, C.H. and Koo, K.S. and Mustafa, Mohd Rais and Ng, S.W. and 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, DOI https://doi.org/10.1016/j.poly.2012.03.014.

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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
Funders:	UNSPECIFIED
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 04:06
Last Modified:	21 Aug 2019 09:18
URI:	http://eprints.um.edu.my/id/eprint/3295

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