Reference

Modulation of superoxide production from murine macrophages by the antitumor agent flavone acetic acid and xanthenone acetic acid analogs

Modulation of superoxide production from murine macrophages by the antitumor agent flavone acetic acid and xanthenone acetic acid analogs. Thomsen, Lindy L.; Baguley, Bruce A.; Ching, Lai Ming; Gavin, John B. (Med. Sch., Univ. Auckland, Auckland, N. Z.). Biochem. Pharmacol., 43(2), 386-9 (English) 1992. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) In this study, the effect of flavone-8-acetic acid (FAA) on superoxide prodn. from murine macrophages in the presence or absence of PMA is described and the effects of FAA with those of xanthenone-4-acetic acid (XAA) derivs. compared. These derivs. include 5,6-MeXAA, the most dose potent of antitumor agents, and 8-MeXAA, an inactive analog. The use of this series with diverse dose potency and activity provides an excellent basis for detg. whether superoxide prodn. correlates with antitumor effects. Thus, comparisons are also made here between the effects of these agents on superoxide prodn. and their antitumor effects against the exptl. s.c. Colon 38 murine tumor. Comparison of in vitro and in vivo effects shows that there is no correlation between the effects of FAA, XAA analogs or indomethacin on superoxide prodn., and their induction of hemorrhagic necrosis or growth delays in s.c. Colon 38 murine tumors. Thus the antiinflammatory activity of these compds. is unrelated to their action against exptl.Except for chemicals metioned above, 117570-47-5 and 117570-53-3 are also used. solid tumor models. .

Plasma pharmacokinetics of the antitumor agents 5,6-dimethylxanthenone-4-acetic acid, xanthenone-4-acetic acid and flavone-8-acetic acid in mice

Plasma pharmacokinetics of the antitumor agents 5,6-dimethylxanthenone-4-acetic acid, xanthenone-4-acetic acid and flavone-8-acetic acid in mice. McKeage, Mark J.; Kestell, Philip; Denny, William A.; Baguley, Bruce C. (Med. Sch., Univ. Auckland, Auckland, N. Z.). Cancer Chemother. Pharmacol., 28(6), 409-13 (English) 1991. CODEN: CCPHDZ. ISSN: 0344-5704. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Although the antitumor agent flavone-8-acetic acid (FAA) exhibits remarkable activity against murine solid tumors, its clin. use has a no. of pharmacol. drawbacks, including low dose potency and dose-dependent pharmacokinetics. Xanthenone-4-acetic acid (XAA) and its 5,6-di-Me deriv. 87626-55-9 and 117570-53-3 which are cas registry numbers are also used here. (5,6-MeXAA) were synthesized during a search for better analogs of FAA. The maximal tolerated doses (MTDs) of 5,6-MeXAA, XAA and FAA in BDF1 mice were 99, 1,090 and 1,300 mmol/kg, resp. At the MTD, 5,6-MeXAA displayed the following pharmacokinetic properties: maximal plasma concn., 600 mm; mean residence time, 4.9 h; AUC, 2,400/h/L; and vol. of steady-state distribution, 0.2 L/kg. All compds. displayed nonlinear elimination kinetics at the MTD, but when the logarithm of the AUC was plotted against that of the delivered dose, the slope of the regression line for 5,6-MeXAA was found to be 1.2 as opposed to 1.4 for XAA and 1.98 for FAA. 5,6-MeXAA thus showed only a slight deviation from dose-independent kinetics. 5,6-MeXAA bound to plasma proteins in a manner similar to that exhibited by FAA, although the plasma concn. of free drug was lower for the former than for the latter. As a consequence, the calcd. maximal free drug concn. for 5,6-MeXAA in plasma was 23 times lower than that for FAA. .