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Propionate and butyrate esters of camptothecin and 9‐nitrocamptothecin as antileukemia prodrugs in vitro
Author(s) -
Han Z.,
Cao Z.,
Chatterjee D.,
Wyche J.,
Pantazis P.
Publication year - 1999
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1999.tb01754.x
Subject(s) - in vitro , chemistry , prodrug , butyrate , propionate , camptothecin , pharmacology , medicine , biochemistry , fermentation
Six camptothecin (CPT) alkyl esters and four 9‐nitrocamptothecin (9NC) alkyl esters were assayed for ability to inhibit proliferation and induce programmed cell death (apoptosis) in human leukemia HL‐60 and U‐937 cells, which exhibit differential sensitivity to CPT and 9NC. In general, CPT‐propionate and CPT‐butyrate demonstrated activities, while the other esters were practically inactive. Similarly, 9NC‐propionate and 9NC‐butyrate were active, while the other 9NC esters exhibited little or no activity. The biologically active esters required metabolic conversion (i.e., de‐esterification) to their parental compounds as demonstrated by the conversion of CPT‐propionate to CPT in mouse liver homogenate, and the topoisomerase I‐inhibition assay. In conclusion, the propionate and butyrate esters of CPT and 9NC are CPT and 9NC prodrugs, that can develop to important chemotherapeutic agents for the effective treatment of human leukemias and other malignancies.