title: Studies on anthracenes. 1. Human telomerase inhibition and lipid peroxidation of 9-acyloxy 1,5-dichloroanthracene derivatives.
abstract: 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.
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC. huanghs@ndmctsgh.edu.tw
authors.forename: H S
authors.initials: HS
authors.lastname: Huang
authors.forename: J M
authors.initials: JM
authors.lastname: Hwang
authors.forename: Y M
authors.initials: YM
authors.lastname: Jen
authors.forename: J J
authors.initials: JJ
authors.lastname: Lin
authors.forename: K Y
authors.initials: KY
authors.lastname: Lee
authors.forename: C H
authors.initials: CH
authors.lastname: Shi
authors.forename: H C
authors.initials: HC
authors.lastname: Hsu
mesh_terms: 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
chemical_list: D000873:Anthracenes; D000880:Anthraquinones; D019098:Telomerase