Dependence of anticancer activity of camptothecins on maintaining their lactone function.
Camptothecins contain a lactone ring that exists in the closed form below ph 7. Above 7, the open (CPT+) and the closed (CPT) form coexist in a 50-50 ratio in mouse plasma and in a 90-10 ratio in human plasma due to the high affinity of human serum albumin (HSA) for CPT+. CPT+ is much less toxic than CPT and it is excreted much faster. In complete RPMI 1640 culture medium, the equilibrium CPT(+)-CPT is 50-50. If 4% HSA is added, it moves to 90-10 modeling for the human physiological situation.
Giovanella
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BC
Stehlin Foundation for Cancer Research, 1918 Chenevert, Houston, Texas 77003, USA.
Harris
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N
Mendoza
J
J
Cao
Z
Z
Liehr
J
J
Stehlin
J S
JS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004355:Drug Stability; D006801:Humans; D007783:Lactones / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D002166:Camptothecin