Synthesis, biological evaluation and DNA binding properties of novel mono and bisnaphthalimides

Braña, Miguel F.; Cacho, Mónica; Ramos, Ana; Domínguez, M. Teresa; Pozuelo, José Manuel; Abradelo, Cristina; Rey-Stolle, Fernanda; Yuste, M.; Carrasco, Carolina; Bailly, Christian

doi:10.1039/b209042b

Cited by 67 publications

(29 citation statements)

References 14 publications

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“…Polyamine derivatives are known as apoptosis inducers (20), and naphthalimide derivatives-induced DNA damage has been widely studied (4,6,7). Many naphthalimide polyamine conjugates have been synthesized as a new type of selective anti-tumor agents.…”

Section: Discussionmentioning

confidence: 99%

“…Present research also reports that linking naphthalimide with a polyamine backbone improves their cytotoxicity (3,9,10) as well as selectivity against tumor cells and normal cells (11). Elinafide, a bisnaphthalimide polyamine derivative with dramatic anti-tumor activity, has been selected and progressed to clinical treatment against solid tumors (7,12). Indeed, many anti-tumor drugs are poorly tumor selective resulting in high incidences of adverse effects.…”

Section: Introductionmentioning

confidence: 89%

“…Many analogues of mononaphthalimide have been designed and synthesized (4), amonafide, one representative mononaphthalimide derivative, has been selected and progressed to clinical treatment (5) but fails to enter phase III. Despite this, a series of analogues of mononaphthalimide have been evaluated in vitro (6,7). UNBS5162, a new analogue of mononaphthalimide, is currently in phase I clinical trial (8).…”

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen species (ROS) accumulation induced by mononaphthalimide-spermidine leads to intrinsic and AIF-mediated apoptosis in HeLa cells

Zhao

2011

Oncol Rep

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Abstract. Developing polyamine conjugates having the potential of transporting naphthalimide selectively into tumor cells is attractive. However, the evaluation of their cytotoxic mechanism has not been comprehensive. This study focused on the effects of mononaphthalimide spermidine (MNISpd) conjugate on apoptosis induction and the relationship between MNISpd-induced apoptosis and reactive oxygen species (ROS) in HeLa cells. Our findings indicated that 9 μM MNISpd induced apoptosis in HeLa cells during a 48-h period. MNISpd induced apoptosis in HeLa cells following cytochrome c release, elevation of caspase 3/9 activity, apoptosisinducing factor (AIF) translocation and up-/down-regulation of Bax/Bcl-2 protein expression, respectively, and these effects were completely antagonized by pre-incubation with 10 mM NAC for 2 h. MNISpd induced significant ROS accumulation following up-regulation of polyamine oxidase (PAO) activity and complex variations in glutathione levels. It is concluded that MNISpd-induced apoptosis is related to intrinsic caspase-dependent and AIF-mediated caspaseindependent apoptosis pathways in HeLa cells. MNISpdinduced apoptosis correlates to MNISpd-induced ROS production resulting from GSH (reduced form of glutathione) pool depletion, and PAO is likely to be the source of ROS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen species (ROS) accumulation induced by mononaphthalimide-spermidine leads to intrinsic and AIF-mediated apoptosis in HeLa cells

Zhao

2011

Oncol Rep

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“…45 The monomer 29a and the bis-naphthalimide 30a were also shown to have strong preference for GC rich DNA sequences. 46 Additionally, derivative 30a was also found to inhibit DNA relaxation by topoisomerase I.…”

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confidence: 99%

“…This has been rationalised in terms of steric hindrance resulting from the presence of two trifluoromethyl groups interfering with the bis-intercalation. 45 Methylation of the two N-atoms of the linker in 30a was found to reduce the binding affinity of the dimer. 46 Binding to major/minor groove of DNA has been probed using oligonucleotides containing modified nucleotides 7-deazaguanine (C 7 -G), 5-methyl cytosine (M) and inosine (I).…”

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confidence: 99%

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

et al. 2013

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The development of functional 1,8-naphthalimide derivatives as DNA targeting, anticancer and cellular imaging agents is a fast growing area and has resulted in several such derivatives entering into clinical trials.This review gives an overview of the many discoveries and the progression of the use of 1,8-naphthalimides as such agents and their applications to date; focusing mainly on mono-, bis-naphthalimide based structures, and their various derivatives (e.g. amines, polyamine conjugates, heterocyclic, oligonucleotide and peptide based, and those based on metal complexes). Their cytotoxicity, mode of action and cell-selectivity are discussed and compared. The rich photophysical properties of the naphthalimides (which are highly dependent on the nature and the substitution pattern of the aryl ring) make them prime candidates as probes as the changes in spectroscopic properties such as absorption, dichroism, and fluorescence can all be used to monitor their binding to biomolecules. This also makes them useful species for monitoring their uptake and location within cells without the use of co-staining. The photochemical properties of the compounds have also been exploited, for example, for photocleavage of nucleic acids and for the destruction of tumour cells.

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Synthesis and Biological Evaluation of New Bischromone Derivatives with Antiproliferative Activity

Szulawska-Mroczek

Szumilak

Szczesio

et al. 2012

Archiv der Pharmazie

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The synthesis of new bischromone derivatives (4a-c and 5a-c) as potential anticancer drugs is described. The difference in the reactivity between 4-oxo-4H-chromene-3-carboxylic acid 2 (or its methyl ester 3) and 4-oxo-4H-chromene-3-carbonyl chloride 1 with three different polyamines: 3,3'-diamino-N-methyldipropylamine (a), 1,4-bis(3-aminopropyl)piperazine (b), 4,9-dioxa-1,12-dodecanediamine (c) resulted in the formation of two different groups of products, compounds 4a-c and 5a-c, designed in agreement with the bisintercalators' structural requirements. The transformation of 4-oxo-4H-chromene-3-carboxylic acid into 2H-chromene-2,4(3H)-diones (5) was confirmed by the NMR and XRD experiments. Compounds 4a and 5a were evaluated in vitro in the highly aggressive melanoma cell line A375. An enhanced induction of apoptosis and cell cycle arrest clearly revealed that compound 5a was more potent than 4a. Compound 5a was also more active in diminishing the adhesive potential of melanoma cells. Current studies support the notion that small changes in the three-dimensional structure of molecules might have a substantial impact on their biological activity.

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Synthesis, biological evaluation and DNA binding properties of novel mono and bisnaphthalimides

Cited by 67 publications

References 14 publications

Reactive oxygen species (ROS) accumulation induced by mononaphthalimide-spermidine leads to intrinsic and AIF-mediated apoptosis in HeLa cells

Reactive oxygen species (ROS) accumulation induced by mononaphthalimide-spermidine leads to intrinsic and AIF-mediated apoptosis in HeLa cells

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

Synthesis and Biological Evaluation of New Bischromone Derivatives with Antiproliferative Activity

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