DNA-directed alkylating agents. 5. Acridinecarboxamide derivatives of (1,2-diaminoethane)dichloroplatinum(II)

J Med Chem. 1992 Aug 7;35(16):2983-7. doi: 10.1021/jm00094a008.

Abstract

A series of acridine-2- and -4-carboxamide-linked analogues of PtenCl2 has been prepared and evaluated for biological activity against several tumor cell lines in vitro and in vivo. The platinum complexes were generally more cytotoxic than the corresponding ligands against wild-type P388 leukemia cells in vitro, with acridine-4-carboxamide complexes being the more effective. In contrast to cisplatin and PtenCl2, the complexes were equally active in vitro against both wild-type and cisplatin-resistant P388 lines. The 4-carboxamide complexes showed high levels of in vivo activity (ILS greater than 100%) against wild-type P388 using a single-dose protocol, and one compound was also significantly active in vivo in a cisplatin-resistant line, against which cisplatin and PtenCl2 are inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemistry
  • Acridines / pharmacology*
  • Alkylating Agents / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • DNA / drug effects*
  • DNA / metabolism
  • Drug Screening Assays, Antitumor
  • Leukemia P388 / drug therapy
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Acridines
  • Alkylating Agents
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • DNA