Structure-activity relationships for substituted 9-oxo-9,10-dihydroacridine-4-acetic acids: analogues of the colon tumour active agent xanthenone-4-acetic acid.
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.
Gamage
S A
SA
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Rewcastle
G W
GW
Atwell
G J
GJ
Baguley
B C
BC
Denny
W A
WA
D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D015195:Drug Design; D051379:Mice; D009336:Necrosis; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000737:chemistry* / Q000494:pharmacology*
D014966:Xanthenes; C066138:xanthenone-4-acetic acid