Archives of Pharmacal Research

, Volume 22, Issue 6, pp 592–607 | Cite as

Effect of the aryl substituent on antitumor activity of 2-substituted-1,4-dihydroxy-9,10-anthraquinones and 2-substitutedanthracene-1,4,9,10-tetraones

  • Nguyen-Hai Nam
  • Guang-Zhu Jin
  • Mai Ngoc Tam
  • Byung-Zun Ahn
Research Articles Medicinal Chemistry


2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-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 activity (T/C, 125–218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-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 onein vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s).

Key words

1,4-dihydroxy-9,10-anthraquinone anthracene-1,4,9,10-tetraones antitumor activity structure-activity relationship 


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Copyright information

© The Pharmaceutical Society of Korea 1999

Authors and Affiliations

  • Nguyen-Hai Nam
    • 1
  • Guang-Zhu Jin
    • 2
  • Mai Ngoc Tam
    • 3
  • Byung-Zun Ahn
    • 1
  1. 1.College of PharmacyChungnam National UniversityTaejonKorea
  2. 2.College of PharmacyYanbiam UniversityYanji, JilinChina
  3. 3.Institute of ChemistryNational Centre of Natural Science and TechnologyHa NoiViet Nam

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