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.
Hasinoff
B B
BB
Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
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