Mitomycin derivatives having unique condensed-ring structures. Their synthesis and antitumor activity

J Antibiot (Tokyo). 1994 Nov;47(11):1312-21. doi: 10.7164/antibiotics.47.1312.

Abstract

A series of mitomycin derivatives 1-3 having unique condensed-ring structures was synthesized and evaluated for their anticellular and antitumor activity. These compounds were synthesized by the Michael addition of 1.3-dicarbonyl compounds to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylenemitosanes (4-6, and 14) and the subsequent cyclization. For the preparation of 1. the allyloxycarbonyl (Aloc) group was employable for the protection of the aziridine (1a-N-H), since the deprotection proceeded without decomposition of the substrates under the mild conditions with Pd(0) and HCO2H-NEt3. Among these structurally unique derivatives, compounds 1a, 1b, 1d and 1e were quite potent against HeLa S3 human tumor cells and sarcoma 180 solid tumor in mice.

MeSH terms

  • Animals
  • HeLa Cells / drug effects
  • Humans
  • Mice
  • Mitomycins / chemical synthesis*
  • Mitomycins / chemistry
  • Mitomycins / pharmacology
  • Sarcoma 180 / drug therapy

Substances

  • Mitomycins