An investigation of 2'-deoxyribonucleoside cyanoboranes in mice for therapeutic safety.
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. LD(50) values were greater than 1000 mg/kg, IP, for all compounds.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products School of Pharmacy, CB# 7360 University of North Carolina Chapel Hill Chapel Hill NC 27599 USA.
Burnham
B S
BS
Rajendran
K G
KG
Chang
J J
JJ
Sood
A
A
Spielvogel
B
B