Table of Contents
Metal-Based Drugs
Volume 1 (1994), Issue 1, Pages 19-30

An Investigation of 2′-Deoxyribonucleoside Cyanoboranes in Mice for Therapeutic Safety

1Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB# 7360, University of North Carolina Chapel Hill, Chapel Hill 27599, NC, USA
2Department of Pathology, School of Medicine, University of North Carolina Chapel Hill, Chapel Hill 27599, NC, USA
3Boron Biologicals, Inc., 533 Pylon Drive, Raleigh 27636-3489, NC, USA

Received 17 May 1993; Accepted 22 June 1993

Copyright © 1994 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.


A standard acute toxicity study was undertaken to assess 2-deoxyribonucleoside cyanoboranes for therapeutic safety. 2-Deoxyribonucleoside cyanoboranes and related derivatives were nontoxic at doses required for anti-neoplastic and hypolipidemic activities. At higher doses (50 and 100 mg/kg/day IP for 7 days), all treated animals survived with slight reductions in total body weight and small decrements in daily food consumption. No clinical chemistry value was elevated to a magnitude suggesting onset of organ specific toxicity. However, agents appeared to modulate subpopulations of white blood cells, i.e.¯, more lymphocytes than PMNs were present in blood from treated animals as determined by differential cell counts. This modulation is correlated with increases in granulomatous foci in the spleen and mesentery of treated animals after 7 days. The kidney was damaged only by Compound 5¯ at 50 and 100 mg/kg/day; Compound 5¯ had the most potent anti-neoplastic activity. The compounds demonstrated no in vitro¯ toxicity against human HCT-8 ileum cells. LD50 values were greater than 1000 mg/kg, IP, for all compounds.