Synthesis of a new class of camptothecin derivatives, the long-chain fatty acid esters of 10-hydroxycamptothecin, as a potent prodrug candidate, and their in vitro metabolic conversion by carboxylesterases.
Five (20S)-10-hydroxycamptothecin derivatives carrying the long-chain fatty acid esters were prepared for the development of a new class of prodrug-type agents. In vitro experiments using three kinds of purified carboxylesterase isozymes from the liver microsomes of rat, pig, and human demonstrated that these derivatives were efficiently metabolized by enzymes compared with CPT-11.
Takayama
H
H
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Watanabe
A
A
Hosokawa
M
M
Chiba
K
K
Satoh
T
T
Aimi
N
N
D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D004952:Esters; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D013552:Swine
D004952:Esters; D005227:Fatty Acids; D011355:Prodrugs; D000077146:Irinotecan; C028098:10-hydroxycamptothecin; D002265:Carboxylic Ester Hydrolases; D002166:Camptothecin