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Comparative properties of the antineoplastic agent, 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II) and related chelates: Linear free energy correlations

✍ Scribed by Donald A. Winkelmann; Yona Bermke; David H. Petering


Publisher
Elsevier Science
Year
1974
Weight
933 KB
Volume
3
Category
Article
ISSN
0006-3061

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✦ Synopsis


The formation constants, reduction potentials. and kinetics of some redox and substitution reactions are reported for a series of bis(thiosemicarbazonato) mpper(II) complexes_ Linear free energy CorreIations are developed using reduction potentials ss the independent variable in the con-cl&ions-The variation in in &TO tumor cell cytotoxicity elicited by the cheIates corresponds well with the distribution of the complexes in these correlations, thereby ptividing an empirical chemical rationale fcr these differences in biological activity. The liiear free energy relationships suggest the operation of a steric factor in the kinetics of the reactions described_ KEY WORDS Linear free energy correlations, antineoplastic agent, comparative chemical and biological properties, stNCtUE!-fUIKtiOn relationships The ligand, 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) , exhibits strong antineoplastic activity in established, solid animal tumors Cl]. An absolute requirement of copper ion for its activity has been demonstrated in these systems [2]. In fact, its copper(I1) chelate, CuKTS, is a potent antitumor agent [3]. However, in the examination of a variety of related ligand structures, using an +n vitro tumor cell system in which * Author to whom correspondence should be addressed.