Synthesis and cytotoxic activity of acronycine derivatives modified at the pyran ring.
Nitration of acronycine (1) and 6-demethoxyacronycine (3) afforded 2-nitroacronycine (2) and 2-nitro-6-demethoxyacronycine (4), respectively. Reduction of 2-nitroacronycine yielded, depending on the conditions, 2-nitro-1,2-dihydroacronycine (5), 2-oxo-1,2-dihydroacronycine oxime (7) or 2-amino-1,2-dihydroacronycine (6). This latter was readily converted into 2-dimethylamino-1,2-dihydroacronycine (8), 2-acetylamino-1,2-dihydro-acronycine (9) and 2-benzoylamino-1,2-dihydroacronycine (10). The cytotoxicity of these compounds was evaluated against L1210 leukemia cells. Compounds 2 and 7 were 300- and 10-fold more potent than acronycine in inhibiting L1210 cell proliferation, respectively. Compound 2 was devoid of antitumor activity against P388 leukemia and C38 colon adenocarcinoma.
Elomri
A
A
Skaltsounis
A L
AL
Michel
S
S
Tillequin
F
F
Koch
M
M
Rolland
Y
Y
Pierré
A
A
Atassi
G
G
D000175:Acronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000175:Acronine