Anthracycline antibiotics, complexation with

The results obtained by various workers employing these several techniques are not in total agreement. It seems clear, however, that the presence of deoxyguanosine residues in DNA is required for binding of Actino-mycin D. Anthracyclines can complex with poly dAT and poly dGdC however, binding of nogalamycin may be favored by dAT pairs while that of daunomycin is not. The presence of cations (Mg" or Cs" ) may play a role in complex formation between the chromomycin antibiotics and DNA. 

Heparin has been reported to complex with a variety of basic species, including biogenic amines and drugs for reviews, see Refs. 10 and 391. For its possible relevance to the pharmacological properties of heparin and complexed species, mention is made here of complexes with histamine392,393 and anthracycline antibiotics.394 C.d. studies on the interaction of basic homopolypeptides with heparin and other glycosaminogly-cans have shown that heparin is able to induce an ordered, helical conformation in the polypeptide.395 397 Similar, and even more dramatic, effects were observed with mixed basic polypeptides, presumed to represent better models for the biologically relevant interactions with plasma proteins.368... 

H. Berg, G. Horn, U. Luthardt and W. Ihn, Interaction of anthracycline antibiotics with biopolymers Part V—Polarographic behavior and complexes with DNA, Bioelectrochem. Bioenerg., 8 (1981) 537-553. 

Complexes of DNA with a drug doxorubicin (also known as adriamycin or hydroxydaunorubi-cin), Dox, used in cancer chemotherapy were studied using the NMR spectroscopy. Dox is an anthracycline antibiotic closely related to natural daunomycin and like all anthracyclines, it works by intercalating DNA. The intercalation of DNA by Dox (Figures 6.71b, 6.72, and 6.73) affects the behavior of bound water. The used concentration of Dox provides interaction of a large number of Dox molecules with each DNA macromolecule. Dox molecules are located in the places occupied by WAW in the slits between neighboring nucleotide planes. 

Iron-containing pharmaceutical compounds are used and developed as anticancer and antibiotic drugs as well as for treatment of iron deficiency. For instance, Mossbauer spectroscopy was used for studying iron complexes with anticancer antibiotics such as anthracyclines [148], adenosine derivatives [149], and cyclin-dependent kinase inhibitors [ISO]. Sharaby analyzed iron complexes of hexachlorocyclodiphosph(V)azanes of sulfaguanidine (H4L) with antimicrobial activity [151]. Recently, some iron-containing complexes with antituberculosis activity were studied using Mossbauer spectroscopy [152,153]. 

Binaphthol (B1N0L)-Ti complexes 100 are found to be effective catalysts in NED D-A reactions. It catalyzes the reaction of 5-hydroxynaphthoquinone with butadienyl acetate in 86 % yield and 96 % ee of cnJo-product. This intermediate is useful in the synthesis of anthracycline antibiotics [86]. 

Complex glycosylated compounds like macrolides, anthracyclines, aureolic acids, cardiac glycosides, orthosomycines and tetronic acids are of considerable scientific as well as pharmaceutical interest. Obviously, each of them is responsible for certain therapeutic effects with respect to different diseases. Anthracyclines and aureolic acids are applied in cancer chemotherapy, orthosomycines are active as antibiotics against Gram-positive bacteria, and the cardiac glycosides are used in the treatment of cardiac insufficiency. 

Overlap Geometry at the Intercalation Site We shall attempt to utilize the nucleic acid base and anthracycline ring proton com-plexation shifts to deduce which anthracycline aromatic ring(s) overlap with nearest neighbor base pairs in the daunomycin poly-(dA-dT) intercalation complex. It should be noted that the nonplanarity of ring A in the antibiotic requires that the aromatic portion of the anthracycline chromophore cannot intercalate with its long axis colinear to the direction of the Watson-Crick hydrogen bonds at the intercalation site as was demonstrated for proflavine-nucleic acid complexes. 

Anthracyclines constitute another complex and bigger family of antibiotics. They mostly occur as glycosides of the anthracyclinones (aglycone residue). They act by intercalation with the DNA in both normal and neoplastic cells. 

A new solvent system consisting of methanol-water (adjusted to pH 2 with phosphoric acid) has been developed for high-performance liquid chromatography (HPLC) of the daunorubicin complex This method in conjunction with TLC is useful for identification of the anthracycline group of antibiotics. 

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