All chemotherapeutic agents currently in use have a narrow window of therapeutic index of 1 to 1.2. Camptothecin ester
compounds are reported to have a wider therapeutic index when being used to treat human xenografts in nude mice. As a continuous
effort in searching for better chemotherapeutic agents for treating cancers, new haloalkyl camptothecin and 9-nitrocamptothecin ester
derivatives 2a-b and 3a-d were prepared by respective acylation of camptothecin 1a and 9-nitrocamptothecin 1b with the corresponding
acylating agents. These new derivatives were tested in vitro against 8 human cancer cell lines using 7 different concentrations ranging
from 5 to 300 nM and also in vivo against various types of human tumor xenografts grown in nude mice. Most of these new compounds
started showing inhibitory effects on the growth of 8 cancer cell lines at concentration of 80 nM and achieved greater than 70%
inhibitions against these cell lines when the concentration increased to 300 nM. Compound 2a and 3a showed good activity against
human tumor xenografts in nude mice. Compared to mother compound camptothecin, 3a was much less toxic in mice with a better
therapeutic index, having the potential to be further developed as a safer treatment for cancers.
Keywords: Anticancer activity, Camptothecin esters, Esterification, Human tumor xenografts, Nude mice, Prodrugs, Therapeutic index, Topoisomerase 1, Toxicity, cytotoxic alkaloidal compound.
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