New analogues of flavone-8-acetic acid were synthesized, bearing an alkoxy group in position 3 and different substituents on the benzene ring in position 2 of the flavone nucleus. The compounds were tested for direct cytotoxicity against four human tumor cell lines and for indirect antitumor effects by measuring their ability to enhance lytic properties of murine macrophages and human monocytes. Though direct toxicity was very low, the compounds were able to induce significant indirect toxicity. Notably, most of them (4c, 4d, 4e, 4f, 4h, 4i, 4m, 4n, and 4o) showed important activity on human monocytes and could be regarded as the first flavone derivatives endowed with such activity. Particularly interesting seem to be compounds 4m and 4n, which showed IC 50 values up to 7 times higher than DMXAA, which has now completed phase I clinical trials.
Gobbi S., Rampa A., Bisi A., Belluti F., Piazzi L., Valenti P., et al. (2003). Synthesis and biological evaluation of 3-alkoxy analogues of flavone-8-acetic acid. JOURNAL OF MEDICINAL CHEMISTRY, 46(17), 3662-3669 [10.1021/jm030771o].
Synthesis and biological evaluation of 3-alkoxy analogues of flavone-8-acetic acid
Gobbi S.
Primo
;Rampa A.;Bisi A.;Belluti F.;Piazzi L.;Valenti P.;
2003
Abstract
New analogues of flavone-8-acetic acid were synthesized, bearing an alkoxy group in position 3 and different substituents on the benzene ring in position 2 of the flavone nucleus. The compounds were tested for direct cytotoxicity against four human tumor cell lines and for indirect antitumor effects by measuring their ability to enhance lytic properties of murine macrophages and human monocytes. Though direct toxicity was very low, the compounds were able to induce significant indirect toxicity. Notably, most of them (4c, 4d, 4e, 4f, 4h, 4i, 4m, 4n, and 4o) showed important activity on human monocytes and could be regarded as the first flavone derivatives endowed with such activity. Particularly interesting seem to be compounds 4m and 4n, which showed IC 50 values up to 7 times higher than DMXAA, which has now completed phase I clinical trials.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
