DNA alkylation by leinamycin can be triggered by cyanide and phosphines.
Previous work has shown that alkylation of DNA by the antitumor agent leinamycin (1) is potentiated by reaction of the antibiotic with thiols. Here, it is shown that other soft nucleophiles such as cyanide and phosphines can also trigger DNA alkylation by leinamycin. Overall, the results suggest that reactions of cyanide and phosphines with leinamycin produce the oxathiolanone intermediate (2), which is known to undergo rearrangement to the DNA-alkylating episulfonium ion 4.
Zang
H
H
Departments of Chemistry and Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.
Breydo
L
L
Mitra
K
K
Dannaldson
J
J
Gates
K S
KS
D000478:Alkylation / Q000187:drug effects; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D003486:Cyanides / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D007769:Lactams; D018942:Macrolides; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D010720:Phosphines / Q000494:pharmacology*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D013844:Thiazoles; D013871:Thiones
D000903:Antibiotics, Antineoplastic; D003486:Cyanides; D007769:Lactams; D018942:Macrolides; D009841:Oligonucleotides; D010720:Phosphines; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin; D004247:DNA