Daunomycin (Daunorubicin) and Adriamycin and Structural Analogues: Biological Activity and Mechanism of Action

Marco, A. Di; Arcamone, F; Zunino, Franco

doi:10.1007/978-3-642-46304-4_8

Cited by 58 publications

(24 citation statements)

References 60 publications

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“…Eliminations of genetic markers of R-factors probably are direct results of inhibitions of plasmidic DNA replicons owing to the DNA-template toxicity of intercalators. Such template toxicities have, indeed, been demonstrated for daunomycin (10), proflavin (17), Nitroakridin 3582 (32), ethidium (29), miracil D (16), quinacrine (23), tilorone (6), quinine (23), and chloroquine (23).…”

Section: Discussionmentioning

confidence: 89%

Elimination of Resistance Determinants from R-Factor R1 by Intercalative Compounds

Hahn

Ciak

1976

Antimicrob Agents Chemother

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Eighteen deoxyribonucleic acid (DNA)-complexing compounds, among them 15 intercalative substances, and, additionally, nalidixic acid eliminated with different frequencies four antibiotic resistance determinants from the R-factor R1, carried by Salmonella typhimurium . Eliminating concentrations did not inhibit growth of the bacteria. The most active compound was “nitroacridine II” {1-diethylamino-3-[(6-nitro-9-acridinyl)amino]propanol}. When 14 compounds which had been tested at a standard concentration of 10 −4 M were listed according to decreasing activities of elimination of the four resistance determinants, a nearly consistent activity sequence was revealed. Frequencies of elimination of the kanamycin resistance determinant correlated directly with the binding of compounds to DNA, i.e., with end points of their displacement of methyl green from the methyl green-DNA complex. We propose that the observed eliminations resulted from selective toxicity for plasmidic template DNA and inhibitions of R-factor replication.

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Section: Discussionmentioning

confidence: 89%

Elimination of Resistance Determinants from R-Factor R1 by Intercalative Compounds

Hahn

Ciak

1976

Antimicrob Agents Chemother

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“…ADG has close similarity to the anthracycline antibiotic daunomycin (DAU) with the daunosamine sugar moiety (figure 1B), which is a potent anticancer drug currently used in clinics [9][10][11][12]. Emerging from DAU some thousand new anthracycline analogs were synthesized in search of stronger biological activity and lower toxicity [13][14][15][16]. A common feature of ADG and DAU is the DNA intercalative binding [10,[17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Drug–DNA binding thermodynamics: A comparative study of aristololactam-β-d-glucoside and daunomycin

Das

Kumar

2012

The Journal of Chemical Thermodynamics

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“…conceptually related method devised by Dr. A. Robbins to select variants presumed to be deficient in general Phagocytosis, by coupling polystyrene beads to a polylysine spacer and thence to daunomycin. This drug inhibits both transcription and translation, presumably because of its ability to intercalate into DNA (19)(20)(21)(22), although a recent report that it can cross-link DNA (23) suggests the possibility ofa slightly different mechanism. We presume that daunomycin is hydrolyzed from the bead and exits from the phagolysosome to the cytoplasm, killing the cell.…”

Section: Discussionmentioning

confidence: 99%

Variants deficient in phagocytosis of latex beads isolated from the murine macrophagelike cell line J774.

Takasaki¹,

Emling²,

Leive³

1984

The Journal of Cell Biology

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Variants that lack the ability to ingest latex beads were isolated from the mouse macrophagelike cell line )774. Carboxylated latex beads were derivatized with polylysine and then daunomycin by a carbodiimide method . Cells that ingested such beads were killed ; variants that survived were isolated . Variants were detected at very low frequency and only after nitrosoguanidine mutagenesis . Of 11 independent isolates, 10 showed a lowered rate of uptake of polystyrene beads (without daunomycin) . All of these proved normal in rate and extent of Fc-mediated phagocytosis. There was essentially no change in sensitivity to free daunomycin in the variants compared to the parent . These results support the previous hypothesis that there are differences in the metabolic routes of receptor-mediated and nonspecific phagocytosis.Phagocytosis, one ofthe important differentiated functions in macrophages, has been grouped into receptor-mediated and receptor-independent or general phagocytosis (1) . Among the receptors that mediate the former process are the Fc receptors which recognize the Fc portion of antibody (2, 3), the C3b receptor that recognizes the C3b fragment of the complement protein C3 (4, 5), and a receptor for fibronectin (6) ; some evidence suggests that the receptor for pinocytosis of mannose, fucose, and N-acetyl-glucosamine-terminated glycoconjugates (7, 8) can also function in phagocytosis (9) . Several previous studies suggest that there are some different essential metabolic steps for receptor-mediated and general phagocytosis, in addition to the obvious lack of receptors for the latter. Thus, Michl et al . (10) showed that under certain conditions 2-deoxyglucose inhibited receptor-mediated phagocytosis, in a mannose-reversible process, but did not inhibit either receptor binding or general phagocytosis . In other experiments, Muschel et al . (11) isolated variants of a macrophagelike cell line that were defective in Fc-mediated phagocytosis although they possessed Fc receptors; such variants were able to phagocytose via general phagocytosis . These findings suggest that some of the processes subsequent to receptor recognition differ for each type of phagocytosis. To study this phenomenon it would be helpful to have variants that are the reverse of the ones found by Muschel et al . (11); in other words, ones that cannot phagocytose via generalized phagocytosis, but can do so via receptor-mediated phagocytosis. We herein report 2198 SEIICHI TAKASAKI, FRANZ EMLING, and LORETTA LEIVE

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Daunomycin (Daunorubicin) and Adriamycin and Structural Analogues: Biological Activity and Mechanism of Action

Cited by 58 publications

References 60 publications

Elimination of Resistance Determinants from R-Factor R1 by Intercalative Compounds

Elimination of Resistance Determinants from R-Factor R1 by Intercalative Compounds

Drug–DNA binding thermodynamics: A comparative study of aristololactam-β-d-glucoside and daunomycin

Variants deficient in phagocytosis of latex beads isolated from the murine macrophagelike cell line J774.

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