Stereoselective hydrolysis of ICRF-187 (dexrazoxane) and ICRF-186 by dihydropyrimidine amidohydrolase.
The enzymatic ring-opening hydrolyses of the doxorubicin cardioprotective agents (+)-(S)-ICRF-187 (dexrazoxane), (-)-(R)-ICRF-186, and rac-ICRF-159 by the enzyme dihydropyrimidine amidohydrolase (DHPase) have been studied. ICRF-187 underwent enzymatic ring-opening hydrolysis by DHPase 4.5 times faster than did ICRF-186. It was also shown that DHPase opens only one ring of ICRF-186 and does not act on this one-ring open hydrolysis product, as has been observed for ICRF-187. Differences in the rates at which the two optical isomers are acted upon by DHPase suggest that they could have differing protective effects.
Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
B B
BB
Hasinoff
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D006868:Hydrolysis; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D011929:Razoxane / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
D011929:Razoxane; D000581:Amidohydrolases; C020047:dihydropyrimidinase