Effects of solute conditions on the relative affinities of the oligonucleotides d(G‐C)<sub>5</sub> and d(A‐T)<sub>5</sub> for the anthracycline drug 2‐fluoro‐4‐demethoxydaunomycin

Hammer, Brendon C.; Russell, Richard A.; Warrener, Ronald N.; Collins, J. Grant

doi:10.1016/0014-5793(89)81198-6

Cited by 4 publications

(4 citation statements)

References 12 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results may indicate a possible low toxicity of ME2303 [77,78]. In pre-clinical studies ME2303 showed interesting characteristic on multidrug-resistant tumor cells, in fact it alone was shown to be effective against drug-resistant human and murine tumor cells [79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96]. Carminomycin is another natural glycosides within the family of anthracyclines.…”

Section: '-Fluoroanthracyclinesmentioning

confidence: 99%

“…This compound was also substituted in position 6, as NO 2 derivative. Warrener and Collins 12 years ago [19], by experiments using 19F NMR, studied the different distribution of the 2-fluoro anthracycline derivative (14) between the oligonucleotides d(G-C)5 and d(A-T)5. They showed that changes in NaCl concentration, as well as the presence of lysine or arginine, affect the equilibrium distribution of the synthetic 2-F anthracycline while varying the pH between 6.2 and 7.7 had no effect.…”

Section: -Fluoro -And 3-fluoroanthracyclines [35]mentioning

confidence: 99%

“…Synthesis and binding properties of conjugates between oligodeoxynucleotides and DAUNO derivatives have been developed [18][19][20][21]. …”

Section: Biological Target Of Anthracyclinesmentioning

confidence: 99%

See 2 more Smart Citations

Fluorinated Anthracyclines: Synthesis and Biological Activity

Giannini

2002

CMC

View full text Add to dashboard Cite

Organic structures with fluorine atom are slightly diffuse in nature. Starting 80s researchers have discovered that the selective introduction of fluorine into biologically active molecules exercised an influence on activity. So an important endeavour in drug design have been described and numerous compounds incorporating fluorine as either a bioisosteric replacement for hydrogen or an isoelectronic replacement for the hydroxyl group have been reported. Parallely, an enormous literature on anthracyclines exists, a class of compounds used in clinical since 70s, as antitumor drugs. Unfortunately, the anthracyclines are known as well for several toxical effects that frequently condition the clinical use. In the last decade a lot of anthracycline derivatives has been described in which has been introduced a fluorine atom in different position of molecule. This review wishes to represent an updated collection of compounds with anthracycline structure where a fluorine atom has been introduced on aglycon or/and sugar moiety. Together with the chemical structures, the synthetic indications are furnished and succinct explanations of biological activity are summarised (if available).

show abstract

Section: '-Fluoroanthracyclinesmentioning

confidence: 99%

Section: -Fluoro -And 3-fluoroanthracyclines [35]mentioning

confidence: 99%

See 1 more Smart Citation

Fluorinated Anthracyclines: Synthesis and Biological Activity

Giannini

2002

CMC

View full text Add to dashboard Cite

show abstract

“…The planar ring is presumably capable of intercalating between the base pairs, and the sugar ring sits in the minor groove (Wang et al, 1987), where it may make contacts with the bases or the backbone chain, thereby helping to anchor the drug. Substitutions, or the removal of functional groups on the aglycon ring, have also led to differences in affinity (Hammer et al, 1989). Compounds with alkyl and halogen substitutions on the sugar ring have been synthesized t Supported by NIH Grants GM21966 and CA28824 and by NIH Postdoctoral Fellowship F32 CA08436 to C.J.R.…”

mentioning

confidence: 99%

Binding affinity and site selectivity of daunomycin analogs

Roche¹,

Berkowitz²,

Sulikowski³

et al. 1994

Biochemistry

View full text Add to dashboard Cite

We have tested a series of daunomycin analogues for binding affinity to a group of oligonucleotides that contain binding sites specific for daunomycin and that were previously screened for relative binding affinity for daunomycin. The series of drugs differed from daunomycin in the sugar moiety, including substitution of a hydroxyl group for the charged amino group and replacement of the 2'-OH by an iodo substituent. Data were analyzed by Scatchard plots and association constants were estimated from the gamma-intercept at saturating levels of oligonucleotide. Because of the solubility problems associated with these compounds, Scatchard plots could not be extended to high levels of binding. A second method of analysis of the fluorescence data confirmed the semiquantitative association constants obtained from the intercepts of the Scatchard plots. The association constants were in the range of 10(5)-10(7) M-1. When compared with daunomycin, the compounds with hydroxyl substituted for the amino group in the sugar ring generally bound less well to the oligonucleotides, by factors of up to several hundred. Much of the binding lost upon removal of the charged amino group was restored, however, with compounds containing an iodo substituent on the sugar ring. Changing the iodo-substituted sugar from the natural L-form to the D-form diminished binding by 6-50-fold, depending on sequence. This result implies a stereospecific interaction of the natural sugar with the DNA chain. A positively cooperative curve was observed in the Scatchard plot for the D-form sugar.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract