Synthesis and cytotoxic and antitumor activity of esters in the 1,2-dihydroxy-1,2-dihydroacronycine series.
Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycine derivatives were more potent than acronycine itself when tested against L1210 cells in vitro. Four selected acronycine derivatives (17,19, 21, and 22) were evaluated in vivo against murine P388 leukemia and colon 38 adenocarcinoma implanted in mice. All compounds were markedly active against P388 at doses 4-16-fold lower than acronycine itself. Against the colon 38 adenocarcinoma, the three compounds 17, 21, and 22 were highly efficient. 1,2-Diacetoxy-1,2-dihydroacronycine (17) was the most active, all the treated mice being tumor-free on day 23.
Elomri
A
A
Laboratoire de Pharmacognosie de l'Université René Descartes, URA au CNRS no. 1310, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Mitaku
S
S
Michel
S
S
Skaltsounis
A L
AL
Tillequin
F
F
Koch
M
M
Pierré
A
A
Guilbaud
N
N
Léonce
S
S
Kraus-Berthier
L
L
Rolland
Y
Y
Atassi
G
G
D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000175:Acronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D004952:Esters / Q000494:pharmacology* / Q000633:toxicity; D007942:Leukemia, Experimental / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D014407:Tumor Cells, Cultured
C102518:1,2-diacetoxy-1,2-dihydroacronycine; D000166:Acridines; D000970:Antineoplastic Agents; D004952:Esters; D000175:Acronine