The Development of New DNA Alkylating Antitumour Agents Modeled on the Natural Product CC-1065

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Author
Primary Supervisor
David Young
Other Supervisors
Wendy Loughlin
Year published
2009
Metadata
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Preliminary studies have revealed that the 4-hydroxyphenethyl halides possess the minimal structural requirements needed to mimic the DNA alkylation profile characteristic to seco-CPI subunits. Subsequent assessment of the 4-aminophenethyl halides showed that these adducts exhibit approximately four times the in vitro cytotoxicity demonstrated by their phenolic counterparts. The incorporation of these simpler compounds into more complex molecules containing non-covalent binding subunits was expected to increase both cytotoxicity and sequence selectivity.
Biological assessment of the synthesized compounds established that the ...
View more >Preliminary studies have revealed that the 4-hydroxyphenethyl halides possess the minimal structural requirements needed to mimic the DNA alkylation profile characteristic to seco-CPI subunits. Subsequent assessment of the 4-aminophenethyl halides showed that these adducts exhibit approximately four times the in vitro cytotoxicity demonstrated by their phenolic counterparts. The incorporation of these simpler compounds into more complex molecules containing non-covalent binding subunits was expected to increase both cytotoxicity and sequence selectivity. Biological assessment of the synthesized compounds established that the simplest compound, 4-aminophenethyl bromide, was a potent antitumor drug which exhibited selectivity for tumor cells over normal fibroblastic cells. This makes 4-aminophenethyl bromide an interesting candidate for further in vivo assessment.
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View more >Preliminary studies have revealed that the 4-hydroxyphenethyl halides possess the minimal structural requirements needed to mimic the DNA alkylation profile characteristic to seco-CPI subunits. Subsequent assessment of the 4-aminophenethyl halides showed that these adducts exhibit approximately four times the in vitro cytotoxicity demonstrated by their phenolic counterparts. The incorporation of these simpler compounds into more complex molecules containing non-covalent binding subunits was expected to increase both cytotoxicity and sequence selectivity. Biological assessment of the synthesized compounds established that the simplest compound, 4-aminophenethyl bromide, was a potent antitumor drug which exhibited selectivity for tumor cells over normal fibroblastic cells. This makes 4-aminophenethyl bromide an interesting candidate for further in vivo assessment.
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Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
School of Biomolecular and Physical Sciences
Item Access Status
Public
Subject
DNA
DNA alkylating antitumor agents
4-aminophenethyl bromide
4-hydroxyphenethyl halide
tumor cells
fibroblastic cells
antitumor drugs