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Dependence of anticancer activity of camptothecins on maintaining their lactone function
B C Giovanella1, N Harris, J Mendoza
1Stehlin Foundation for Cancer Research, 1918 Chenevert, Houston, Texas 77003, USA.
Abstract:
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.
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