Telomerase inhibition by 3'-azido-2', 3'-dideoxynucleoside 5'-triphosphates and telomere shortening in human cultured cells by the corresponding nucleosides.
Telomerase is believed to be a good target for the development of antitumor agents. In this study, 3'-azido-2',3'-dideoxy-2-aminoadenosine (AZddAA), 3'-azido-2',3'-dideoxyadenosine (AZddA), 9-(3-azido-2,3-dideoxy-beta-D-ribofuranosyl)-2-aminopurine (AZddAP), 3'-azido-2-chloro-2',3'-dideoxyadenosine (AZddClA) and their triphosphate derivatives were synthesized. Telomerase assay studies showed that the 2-amino group plays an important role in the inhibitory activity of these compounds. In addition, AZddAA was found to cause telomere shortening in of HL60 cells in culture.
Yamaguchi
Toyofumi
T
Department of Biosciences, Teikyo University of Science and Technology, Uenohara, Yamanashi 409-0193, Japan.
Liu
Xiaohong
X
Ogawara
Tsukasa
T
Inomata
Motoko
M
Saneyoshi
Mineo
M
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001386:Azides / Q000737:chemistry / Q000494:pharmacology; D003854:Deoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D015224:Dideoxynucleosides / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000187:drug effects*
D000970:Antineoplastic Agents; D001386:Azides; D003854:Deoxyribonucleotides; D015224:Dideoxynucleosides; D004791:Enzyme Inhibitors; D019098:Telomerase