Synthesis and biological evaluation of 3-alkoxy analogues of flavone-8-acetic acid.
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
Silvia
S
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. sigobbi@alma.unibo.it
Rampa
Angela
A
Bisi
Alessandra
A
Belluti
Federica
F
Piazzi
Lorna
L
Valenti
Piero
P
Caputo
Anna
A
Zampiron
Antonella
A
Carrara
Maria
M
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; C049328:flavone acetic acid