Synthesis and biological activity of esters in the trans-1,2-dihydroxy-1,2-dihydroacronycine series.
Permanganate oxidation of acronycine (1) led to keto alcohol 4 which could be reduced to trans-1,2-dihydroxy-1,2-dihydroacronycine (3) using NaBH4. Acylation of 3 afforded 12, 13, and 14. These esters (12, 13, and 14) were more potent than 1 when tested against L-1210 cells in vitro. Diacetate 12 was evaluated in vivo against murine P-388 leukemia and was markedly active at a dose 16-fold lower than acronycine itself. Comparison of these results with those recently obtained in the cis-1,2-dihydroxy-1,2-dihydroacronycine series is discussed.
Magiatis
P
P
Laboratory of Pharmacognosy, University of Athens, Greece.
Mitaku
S
S
Skaltsounis
A L
AL
Tillequin
F
F
Koch
M
M
Pierré
A
A
Atassi
G
G
D000175:Acronine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D010946:Plants, Medicinal / Q000737:chemistry*; D014407:Tumor Cells, Cultured
C111686:1,2-dihydroxy-1,2-dihydroacronycine; D000972:Antineoplastic Agents, Phytogenic; D000175:Acronine