Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors

Filosa, Rosanna; Peduto, Antonella; Micco, Simone Di; Caprariis, P. De; Festa, Michela; Petrella, Antonello; Capranico, Giovanni; Bifulco, Giuseppe

doi:10.1016/j.bmc.2008.11.024

Cited by 110 publications

(53 citation statements)

References 19 publications

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“…These interactions can lead to higher van der Waals interactions with the DNA functional groups which define the stability of the groove, making the AT regions more preferable regions of the dodecamer. 44 Complexes exhibited additional stabilization through the strong intermolecular hydrogen bonding interaction between the C-2 carbonyl oxygen of T and the N-3 nitrogen of A. The best binding pose in the AT stretches of the minor groove was indicative of an extensive H-bonding network.…”

Section: Interactions Of Pt(ii) Complexes With Dnamentioning

confidence: 97%

A new class of platinum(ii) complexes with the phosphine ligand pta which show potent anticancer activity

Živković

Kljun

Ilić-Tomič

et al. 2018

Inorg. Chem. Front.

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The anticancer potential of sixteen platinum(II) complexes with general formulae [PtCl(hq)(S-dmso)] (1a-8a) and [PtCl(hq)(pta)] (1b-8b) (where hq is 5-chloro-7-iodo-8-quinolinol (clioquinol; cqH) (1a, 1b), 8-hydroxy-5-nitroquinoline (nitroxoline; nxH) (2a, 2b), 5,7-dichloro-8-quinolinol (3a, 3b), 5,7-diiodo-8-quinolinol (4a, 4b), 5,7-dibromo-8-quinolinol (5a, 5b), 5,7-dichloro-8-hydroxy-2-methyl-quinoline (6a, 6b), 8-hydroxyquinoline (7a, 7b) and 8-quinolinethiol (8a, 8b); dmso is dimethyl sulfoxide and pta is 1,3,5-triaza-7-phosphaadamantane) was determined through in vitro cytotoxicity assay in human fibroblasts (MRC5) and two carcinoma cell lines (A375 and A549) and embryotoxicity assay in a zebrafish model. Interactions with double stranded DNA through in vitro assay and a molecular docking study were examined. All complexes, except 6a, exhibited a high cytotoxic effect on MRC5 cells at a concentration of 10 µg mL −1 while 1b, 5a, 6a and 3b showed selective toxicity towards carcinoma cell lines. In general, were 1b, 3b, 6b and 5b. From observations of the DNA interaction ability and of the in silico assessment, no apparent DNA fragmentation was observed either on DNA extracted from the treated cancer cell line or from the zebrafish embryos.

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Section: Interactions Of Pt(ii) Complexes With Dnamentioning

confidence: 97%

A new class of platinum(ii) complexes with the phosphine ligand pta which show potent anticancer activity

Živković

Kljun

Ilić-Tomič

et al. 2018

Inorg. Chem. Front.

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“…The docked structures shown in Figure 9 corroborate well with the experimental results and clearly indicate that the compound 1 fits snugly into the curved contour of the targeted DNA in the minor groove and is situated within a G-C rich region, thus leading to Van der Waals interaction and hydrophobic contacts with the DNA functional groups that define the groove. [34] In addition to this the phenyl ring of the compound 1 is arranged in an intercalative manner between the G10A and C11A of strand A of the DNA double helix. In this configuration, the N14 of the compound remains inclined towards the phosphodiester bond of DNA and hence the possibility of hydrogen bonding cannot be ruled out.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Synthesis, Crystal Structure and in vitro DNA Binding Studies of Combretastatin A-4 Analogue

Rizvi¹,

Dangat²,

Yaseen³

et al. 2015

Croat. Chem. Acta

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Synthesis of a novel Combretastatin A-4 analogue using Schiff's reaction of benzil and 4-aminoantipyrine has been achieved under solvent free conditions. The structure of compound was examined spectroscopically and confirmed from single crystal diffraction studies. The synthesized Combretastatin A-4 analogue was investigated for its DNA binding ability as the plausible mechanism for its antitumor activity. The binding propensity of the synthesized compound with calf-thymus (CT) DNA was monitored with absorption and emission spectrophotometric titrations. The calculations predict a binding constant of 7.24 × 10 4 for the complex of the synthesized compound with CT DNA which is comparable in magnitude to that of DNA binding of bactericidal drug enoxacin and typical intercalation indicator ethidium bromide (EB). Competitive binding studies of the synthesized compound with EB using fluorescence titration reveal that it displaces the DNA-bound EB and binds in intercalative mode which was further supported by circular dichroism (CD) spectroscopy. The probable site and binding energy of the compound with DNA was further theoretically investigated by molecular docking studies. The significant DNA binding ability of the synthesized Combretastatin A4 analogue as revealed from this study could be related to the anticancer activity of the Combretastatin A4.

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“…However, the main application to date for the naphthalimides, is their potential as therapeutic agents [7] especially in the area of cancer therapy. The flat aromatic structural of the naphthalimido ring and its ability to bind to DNA by intercalation are attractive features that had attracted much attention in the development of new mono naphthalimides [8][9] and bisnaphthalimido [10][11] derivatives for enhanced anticancer activities and aqueous solubility. Among the mononaphthalimido derivatives, Mitonafide and analogues had reached clinical trial but failed to progress due to unpredicted neurological toxicity side effects [12].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of New Naphthalimides as Potential Anticancer Agents against Breast Cancer MCF-7, Pancreatic Cancer BxPC-3 and Colon Cancer HCT- 15 Cell Lines

Noro¹

2015

Organic Chem Curr Res

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Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors

Cited by 110 publications

References 19 publications

A new class of platinum(ii) complexes with the phosphine ligand pta which show potent anticancer activity

A new class of platinum(ii) complexes with the phosphine ligand pta which show potent anticancer activity

Synthesis, Crystal Structure and in vitro DNA Binding Studies of Combretastatin A-4 Analogue

Evaluation of New Naphthalimides as Potential Anticancer Agents against Breast Cancer MCF-7, Pancreatic Cancer BxPC-3 and Colon Cancer HCT- 15 Cell Lines

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