Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin Journal Article

  


Authors: Koyama, M.; Takahashi, K.; Chou, T. C.; Darzynkiewicz, Z.; Kapuscinski, J.; Kelly, T. R.; Watanabe, K. A.
Article Title: Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin
Abstract: Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells. Representative compounds were spectrophotometrically studied for their capacity to interact with natural and denatured DNA. In general, those anthraquinones bearing an amino function interact with DNA. 1,8-Dimethoxyanthraquinones are incapable of intercalating into DNA. 1- or 8-Monohydroxymono-methoxyanthraquinones, however, interact with DNA to some extent. No straightforward correlation is apparent between the DNA-affinity data of the compounds studied spectrophotometrically and their cytotoxic effects. Cytotoxic potencies of these compounds on cell growth inhibition during a 72-h period are inversely correlated to their potencies when inhibiting [3H]TdR incorporation into DNA during the initial 30 min of exposure. Surprisingly, some compounds that showed more cytotoxicity did not inhibit initial TdR incorporation (0–30 min), while some others that strongly inhibited TdR incorporation initially did not exhibit cytotoxicity in 72 h. The results suggest that the cytotoxicity produced by these compounds is time dependent and is not a direct result of initial inhibition of DNA replication. © 1989, American Chemical Society. All rights reserved.
Keywords: leukemia; unclassified drug; human cell; nonhuman; antineoplastic agents; dna synthesis; animal cell; animal; mice; cytotoxicity; drug screening; tumor cells, cultured; drug synthesis; structure activity relation; leukemia, promyelocytic, acute; chemistry; dna; cell culture; dna, neoplasm; dna binding; spectrum analysis; emodin; anthraquinones; spectrophotometry; leukemia l1210; intercalating agents; human; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; chrysophanic acid derivative; emodin derivative
Journal Title: Journal of Medicinal Chemistry
Volume: 32
Issue: 7
ISSN: 0022-2623
Publisher: American Chemical Society  
Date Published: 1989-07-01
Start Page: 1594
End Page: 1599
Language: English
DOI: 10.1021/jm00127a032
PUBMED: 2738893
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0024410607&doi=10.1021%2fjm00127a032&partnerID=40&md5=b469611e6ed0068daa03c2f65f785064
Notes: Article -- Export Date: 14 April 2020 -- Source: Scopus
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MSK Authors
  1. Ting-Chao Chou
    319 Chou
  2. Kyoichi A Watanabe
    125 Watanabe
  3. Zbigniew Darzynkiewicz
    61 Darzynkiewicz
  4. Jan Kapuscinski
    17 Kapuscinski
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