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.
authors.affiliation: Sloan-Kettering Institute for Cancer Research, Sloan-Kettering Division of Graduate School of Medical Sciences, Cornell University, New York, New York 10021.
authors.forename: M
authors.initials: M
authors.lastname: Koyama
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: Z
authors.initials: Z
authors.lastname: Darzynkiewicz
authors.forename: J
authors.initials: J
authors.lastname: Kapuscinski
authors.forename: T R
authors.initials: TR
authors.lastname: Kelly
authors.forename: K A
authors.initials: KA
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D004642:Emodin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D007364:Intercalating Agents; D007939:Leukemia L1210 / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D051379:Mice; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D004247:DNA; D004642:Emodin; C027113:chrysophanic acid