Synthesis and cytotoxicity studies of 8-amino-6-methyl-2-beta-D-ribofuranosyl-1,2,3,5,6,7-hexaazaacenaphthyle ne (7-aza-TCN) and the corresponding 2'-deoxy- and arabinonucleoside analogues.
The tricyclic nucleoside 8-amino-6-N-methyl-2-beta-D-ribofuranosyl-1,2,3,5,6, 7-hexaazaacenaphthylene was synthesized from 8-amino-6-N-methyl-4-(methylthio)-2-beta-D-ribofuranosyl-1,2,3,5,6, 7-hexaazaacenaphthylene. The 2'-deoxy analogue of 5, 8-amino-6-N-methyl-2-(2-deoxy-beta-D-ribofuranosyl)-1,2,3,5,6, 7-hexaazaacenaphthylene (11), and the arabino analogue of (5), 8-amino-6-N-methyl-2-beta-D-arabinofuranosyl-1,2,3,5,6, 7-hexaazaacenaphthylene (14) were synthesized from 5. Nucleosides 2,3,4,5,11, and 14 were evaluated for potential anticancer activity by measuring their ability to inhibit the growth of L1210 and H. Ep. 2 tumor cells in vitro.
Kawasaki
A M
AM
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Wotring
L L
LL
Townsend
L B
LB
D000073:Acenaphthenes; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D015649:Pentostatin / Q000494:pharmacology; D010766:Phosphorylation; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000073:Acenaphthenes; D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D012263:Ribonucleosides; C051669:8-amino-6(N)-methyl-2-ribofuranosyl-1,2,3,5,6,7-hexaazaacenaphthylene; D015649:Pentostatin