Bis-daunomycin hydrazones: Interactions with DNA

Phillips, Don R.; Brownlee, Robert T. C.; Reiss, J. A.; Scourides, Panayiotis A.

doi:10.1007/bf00873121

Cited by 13 publications

(9 citation statements)

References 20 publications

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“…In order to increase the drug affinity towards DNA, and hopefully to increase the specificity as well, attempts have been made to produce bis-intercalating daunorubicin, first via the C13-C14 position [53] and later by the C-4' or C3' position [54]. The former approach disturbed the DNA binding activity whereas the latter approach was successful in producing bis-daunorubicin named WP631 (Fig.…”

Section: Daunorubicin Dimermentioning

confidence: 98%

Novel Classes of Dimer Antitumour Drug Candidates

Chow¹,

Chan

2009

CPD

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Polyvalency in the biological world is defined as the simultaneous binding of multiple ligands to one receptor. Polyvalency can increase the affinity of the polyvalent ligand by 100-1000 fold over the monovalent ligand. Such phenomenon has been employed to design polyvalent toxin inhibitors. Bivalency is a similar approach where two ligands are joined together with a linker to form a homo- or hetero-dimer with an increase in affinity by up to several hundred fold over the monovalent ligand. This review will summarize the recent advancement in designing bivalent inhibitors to be used as antitumour agents. Some dimers (e.g. artemisinin homo-dimer) simply increase the affinity of the monovalent ligands without detailed knowledge of the target. Other dimers are designed with well-characterized targets, for example, jesterone dimer (inhibiting Rel/NF-kappaB) and 3,3'-diindolymethane and their derivatives (inhibiting Akt and NFkappaB). Some dimers are designed based on the high definition structure between ligand and target (e.g. benzodiazepine and daunorubicin interacting with DNA). Heterodimers have also been produced by combining either two different antitumor drugs (e.g. cis-platin/acridine or cis-platin/naphthalimide) or combining one antitumor candidate (artemisinin) with a molecule which can increase the efficacy of the former (transferrin receptor). Finally we will discuss the design of bivalent inhibitors of the P-glycoprotein (ABCB1; MDR or P-gp) to overcome the problem of antitumor resistance.

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Section: Daunorubicin Dimermentioning

confidence: 98%

Novel Classes of Dimer Antitumour Drug Candidates

Chow¹,

Chan

2009

CPD

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“…10 Moreover, various analogs of 4-hydroxypyran-2-ones have been reported to inhibit HIV protease, one of the crucial key enzymes essential for the replication of HIV. 11,12 Having this in mind we thought that heterocycles, which contain a boron atom in their backbone, in addition to the pyrone ring of DHA, might exhibit interesting biological activities.…”

Section: Introductionmentioning

confidence: 99%

“…13 Furthermore, 4-pyrimidone hydrazone derivatives exhibit excellent activity against wild-type HIV-1, 14 whereas fluorescein and bis-daunomycin hydrazone derivatives are characteristic examples of hydrazones that have been reported to interact with DNA. 12,15 Based on the above literature information and on our continuing interest in hydrazono substrates 21 we designed the synthesis of novel pyranone-fused boron heterocycles of type 6 (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel dehydroacetic acid N -aroylhydrazone-derived boron heterocycles

et al. 2015

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“…There have been a number of attempts to produce bis‐intercalating daunorubicin derivatives, with increased affinity for DNA. In early studies these were linked through C13 and C14 as these are chemically accessible [20,21]. However these positions are involved in DNA binding and the modifications decreased the affinity of each monomer.…”

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confidence: 99%

Sequence selective binding of bis‐daunorubicin WP631 to DNA

Fox

Webster

Phelps

et al. 2004

European Journal of Biochemistry

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We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the bis-daunorubicin antibiotic WP631 with DNA. The ligand produces clear DNase I footprints that are very different from those seen with other anthracycline antibiotics such as daunorubicin and nogalamycin. Footprints are found in a diverse range of sequences, many of which are rich in GT (AC) or GA (TC) residues. As expected, the ligand binds well to the sequences CGTACG and CGATCG, but clear footprints are also found at hexanucleotide sequences such GCATGC and GCTAGC. The various footprints do not contain any particular unique di-, tri-or tetranucleotide sequences, but are frequently contain the sequence (G/C)(A/T)(A/T)(G/C). All sequences with this composition are protected by the ligand, though it can also bind to some sites that differ from this consensus by one base pair.

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Bis-daunomycin hydrazones: Interactions with DNA

Cited by 13 publications

References 20 publications

Novel Classes of Dimer Antitumour Drug Candidates

Novel Classes of Dimer Antitumour Drug Candidates

Synthesis of novel dehydroacetic acid N -aroylhydrazone-derived boron heterocycles

Sequence selective binding of bis‐daunorubicin WP631 to DNA

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