SYNTHESIS AND CYTOTOXIC ACTIVITY OF ACRONYCINE DERIVATIVES MODIFIED AT THE PYRAN RING

Nitration of acronycine (1) and 6-demethoxyacronycine (3) afforded 2-n itroacronycine (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 conv erted 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 leuk emia cells. Compounds 2 and 7 were 300- and 10-fold more potent than a cronycine in inhibiting L1210 cell proliferation, respectively, Compou nd 2 was devoid of antitumor activity against P388 leukemia and C38 co lon adenocarcinoma.