Archives of Pharmacal Research
- Volume 22 Issue 6
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- Pages.592-607
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- 1999
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- 0253-6269(pISSN)
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- 1976-3786(eISSN)
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
- Nam, Nguyen-Hai (College of Pharmacy, Chungnam National University) ;
- Jin, Guang-Zhu (College of Pharmacy, Yanbiam University) ;
- Tam, Mai-Ngoc (Institute of Chemistry, National Centre of Natural Science and Technology) ;
- Ahn, Byung-Zun (College of Pharmacy, Chungnam National University)
- Published : 1999.12.01
Abstract
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
Keywords
- 1,4-dihyroxy-9,10-anthraquinone, anthracene-1,4,9,10-tetracones, antitumor activity;
- structure-activity relationship