DNA cleavage potency, cytotoxicity, and mechanism of action of a novel class of enediyne prodrugs.
We have discovered a novel class of (E)-3-acyloxy-4-(arylmethylidene)cyclodeca-1,5-diynes which exhibit promising enediyne-like DNA cleavage and cytotoxic activities. LC-MS analysis of the incubation mixture (pH 8.5, 37 degrees C) confirmed formation of 10-membered ring enediyne presumably via an allylic cation and suggested that the 1,4-benzenoid diradical might be one of the active species for DNA damage and cytotoxicity.
Dai
Wei-Min
WM
Lai
Kwong Wah
KW
Wu
Anxin
A
Hamaguchi
Wataru
W
Lee
Mavis Yuk Ha
MY
Zhou
Ling
L
Ishii
Atsushi
A
Nishimoto
Sei-ichi
S
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004278:DNA, Superhelical / Q000737:chemistry*; D006844:Hydrocarbons, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000480:Alkynes; D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D006844:Hydrocarbons, Cyclic; D011355:Prodrugs