Dependence of Anticancer Activity of Camptothecins on Maintaining Their Lactone Function

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.