Potential antitumor agents. 58. Synthesis and structure-activity relationships of substituted xanthenone-4-acetic acids active against the colon 38 tumor in vivo.
In a search for compounds related to flavoneacetic acid with activity against solid tumors, a series of methyl-, methoxy-, chloro-, nitro-, and hydroxy-substituted xanthenone-4-acetic acids have been synthesized and evaluated against subcutaneously implanted colon adenocarcinoma 38 in vivo, using a short-term histology assay as a primary screening system. A major goal of this work was to identify compounds with similar profiles of activity to that of flavoneacetic acid but of higher potency. The level of activity of the compounds appeared to depend more on the nature of the substituent than its positioning, in the order Cl greater than Me, OMe greater than NO2, OH. However, the potency of the compounds was related much more to the position rather than the nature of the substitution, with 5-substituted compounds being clearly the most dose potent. 5-Methylxanthenone-4-acetic acid has a similar level of activity to that of flavoneacetic acid in the test systems employed but is more than 7-fold as dose potent.
Rewcastle
G W
GW
Cancer Research Laboratory, University of Auckland School of Medicine, Private Bag, New Zealand.
Atwell
G J
GJ
Baguley
B C
BC
Calveley
S B
SB
Denny
W A
WA
D000085:Acetates / Q000138:chemical synthesis / Q000627:therapeutic use*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002713:Chlorine; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006900:Hydroxylation; D008745:Methylation; D051379:Mice; D009574:Nitro Compounds; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000138:chemical synthesis / Q000627:therapeutic use*
D000085:Acetates; D009574:Nitro Compounds; D014966:Xanthenes; D002713:Chlorine