Studies on anthracenes. 1. Human telomerase inhibition and lipid peroxidation of 9-acyloxy 1,5-dichloroanthracene derivatives.
The synthetically useful approaches to 9-acyloxy 1,5-dichloroanthracene derivatives are reported. The system selectively reduces the carbonyl group flanked by the peri substituents of the anthracenediones to give the corresponding 1,5-dichloro-9(10H)-anthracenone. Simple regioselective acylation of anthracenone is applied with appropriate acyl chlorides in CH2Cl2 with catalytic amount of pyridine to give the novel 9-acyloxy 1,5-dichloroanthracene derivatives. Considerable interest has developed in the mechanism of how anthracenone achieves this desirable selectivity. In an attempt to understand the mechanism of this reaction, solid-state structures of anthracene derivatives have been obtained. In addition, the inhibition of lipid peroxidation in model membranes was determined as was their ability to inhibit the telomere-addition function of the human telomerase enzyme together with their inhibition of the Taq polymerase enzyme. In contrast to (+)-alpha-tocopherol, 3b, 3c, 3d, 3g, and 3i do not enhance lipid peroxidation in model membranes. Implications for 9-acyloxy 1,5-dichloroanthracene analogues as potential anticancer agents are discussed.
Huang
H S
HS
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC. huanghs@ndmctsgh.edu.tw
Hwang
J M
JM
Jen
Y M
YM
Lin
J J
JJ
Lee
K Y
KY
Shi
C H
CH
Hsu
H C
HC
D000215:Acylation; D000818:Animals; D000873:Anthracenes / Q000737:chemistry / Q000494:pharmacology*; D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000873:Anthracenes; D000880:Anthraquinones; D019098:Telomerase