Table of Contents
Metal-Based Drugs
Volume 4, Issue 2, Pages 89-95
http://dx.doi.org/10.1155/MBD.1997.89

Antineoplastic and Cytotoxic Activities of Nickel(II) Complexes of Thiosemicarbazones

1Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, North Carolina, USA
2Department of Chemistry, Illinois State University, Normal 61761, Illinois, USA

Received 27 February 1997; Accepted 10 March 1997

Copyright © 1997 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nickel(II) complexes of thiosemicarbazons were observed to be potent cytotoxic agents in human and rodent tissue cultured tumor cells. Each compound demonstrated a slightly different profile in the various histological types of tumors. The nickel complex of Appip demonstrated the most potent in vivo activity in the Ehrlich ascites carcinoma. This agent selectively inhibited L1210 DNA and purine syntheses, and DNA polymerase α, PRPP-amido transferase, IMP-dehydrogenase, dihydrofolate reductase, TMP-kinase and thymidylate synthetase activities. L1210 DNA strand scission was evident and DNA viscosity was reduced after 24 hr incubation. The nickel complexes were not L1210 DNA topoisomerase II inhibitors.