Synthesis and cytotoxic activity of acronycine derivatives modified at the pyran ring

Chem Pharm Bull (Tokyo). 1996 Nov;44(11):2165-8. doi: 10.1248/cpb.44.2165.

Abstract

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.

MeSH terms

  • Acronine / analogs & derivatives*
  • Acronine / chemical synthesis*
  • Acronine / pharmacology
  • Adenocarcinoma / drug therapy
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Colonic Neoplasms / drug therapy
  • Drug Screening Assays, Antitumor
  • Leukemia L1210 / drug therapy
  • Leukemia P388 / drug therapy
  • Mice
  • Mice, Inbred Strains
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Acronine