Table of Contents
Metal-Based Drugs
Volume 4, Issue 4, Pages 229-241

Cytotoxic Action of Carboxyborane Heterocyclic Amine Adducts

1Division Medicinal Chemistry, School of Pharmacy, University of North Carolina, Chapel Hill 27559, North Carolina, USA
2Boron Biologicals, Inc., 620 Hutton St, Suite 104, Raleigh 27606, North Carolina, USA

Received 15 May 1997; Accepted 28 May 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.


The heterocyclic carboxyborane amines were found to be potent cytotoxic agents in the murine L1210 lymphoid leukemia and human HeLa suspended carcinoma cells. These agents were observed to inhibit HeLa DNA topoisomerase II activity ~ 200 μM and L1210 topoisomerase II activity ≥ 100 μM. These agents did not cause DNA protein linked breaks themselves, but upon incubation for 14-24 hr did enhance the ability of VP-16 to cause cleavable complexes. The heterocyclic amineboranes inhibited DNA synthesis and caused DNA strand scission. They were additive with VP-16 in affording these results as well as inhibiting colony growth of L1210 cells after co-incubation for 1 hr. The agents inhibited in vitro PKC phosphorylation of both L1210 lymphoid leukemia and human topoisomerase II enzyme.