Search

In an effort to develop novel anti-tumor, or cancer chemopreventive agents, a series of 2',5'-dialkoxylchalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde. In vitro screening revealed low micromolar activity (IC(50)) against several human cancer cell lines. Selective compound 10 induced an accumulation of A549 cells in the G(2)/M phase arrest which was well correlated with inhibitory activity against tubulin polymerization. Cytotoxic compounds 3 and 12 showed significant inhibitory effects on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage-like cells while cytotoxic compound 10 revealed potent inhibitory effect on TNF-alpha formation in RAW 264.7 cells in response to LPS. Compounds 3 and 10 also showed significant inhibitory effects on xanthine oxidase. The present results suggested that compounds 3 and 10 were potential to be served as cancer chemopreventive agents.

In previous paper, we have reported the synthesis and the cytotoxic effect of 1,3-dihydroxy-9,10-anthraquinone derivatives. For further design of more potent compounds, a new series of 1-hydroxy-3-(3-alkylaminopropoxy)-9,10-anthraquinones and 3-(3-alkylaminopropoxy)-9,10-anthraquinones have been synthesized. The cytotoxicity of synthetic compounds were evaluated against human Hep G2, Hep 3B and HT-29 cells. Almost all compounds indicated significant inhibitory activity against Hep G2, Hep 3B and HT-29 cell lines in vitro. Compound 5 exhibited selective cytotoxicity against Hep G2 in a concentration-dependent manner with ED50 value of 1.23 +/- 0.05 microM. Structure-activity analysis revealed that most of the 1-hydroxy-3-(3-alkylamino-2-hydroxypropoxy)-9,10-anthraquinone showed stronger cytotoxic effects than those of 1-hydroxy-3- or 3-(3-alkylaminopropoxy)-9,10-anthraquinones against Hep 3B cell line in vitro. A sub-G1 cell stage and DNA fragmentation in MCF-7 cells were significantly observed after 72 h incubation with selective compound 16. The results show that 16 causes cell death by apoptosis.