Structure-activity relationships for substituted 9-oxo-9,10-dihydroacridine-4-acetic acids: analogues of the colon tumour active agent xanthenone-4-acetic acid

Anticancer Drug Des. 1992 Oct;7(5):403-14.

Abstract

A series of 9-oxo-9,10-dihydroacridine-4-acetic acids (acridone-4-acetic acids) were prepared by Jourdan-Ullmann condensation of 2-halobenzoic acids with 2-aminophenylacetic acids, followed by H2SO4-induced cyclodehydration of the resulting 2-[2-(carboxymethyl)phenylamino]benzoic acids. These were evaluated for their ability to induce haemorrhagic necrosis in transplanted colon 38 tumours in mice, using a short-term histology assay. The results broadly paralleled those seen previously for xanthenone-4-acetic acids, with 1-, 2- and 7-substitution being dystherapeutic, and substitution at the 5- and 6-positions by lipophilic groups increasing activity. While some analogues were as active as xanthenone-4-acetic acids in the histology assay and gave significant growth delays against colon 38 tumours in vivo, as a class the 9-oxo-9,10-dihydroacridine-4-acetic acids were generally less potent than the xanthenone-4-acetic acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • Drug Design*
  • Mice
  • Necrosis
  • Structure-Activity Relationship
  • Xanthenes / chemistry*
  • Xanthenes / pharmacology*

Substances

  • Xanthenes
  • xanthenone-4-acetic acid