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KMID : 0043319990220060592
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Archives of Pharmacal Research
1999 Volume.22 No. 6 p.592 ~ p.607
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Effect of the Aryl Substituent on Antitumor Activity of 2-Substituted-1,4-dihydroxy-9,10-anthraquinones and 2-Substituted-anthracene-1,4,9,10-tetraones
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Nam Nguyen-Hai
Jin Guang Zhu
Tam Mai-Ngoc
Ahn Byung-Zun
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Abstract
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2-(1-Aryl-1-hydroxymethyl)-and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthraceneactivity (T/C 125~128%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-dydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in viv-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor o among the same series, it showed an value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthrancene1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s).
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KEYWORD
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1,4-dihyroxy-9, 10-anthraquinone, anthracene-1,4,9, 10-tetracones, antitumor activity, structure-activity relationship
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