Design, synthesis and biological evaluation of new naphtalene diimides bearing isothiocyanate functionality

Minarini, Anna; Milelli, Andrea; Tumiatti, Vincenzo; Ferruzzi, Lorenzo; Márton, Melinda-Rita; Turrini, Eleonora; Hrelia, Patrizia; Fimognari, Carmela

doi:10.1016/j.ejmech.2011.12.003

Cited by 15 publications

(18 citation statements)

References 38 publications

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“…We have previously reported that CM9 caused a strong drop in ΔΨm. That was demonstrated by a number of cells with decreased mitochondrial potential of about 100% [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

“…As CM9 was previously found to inhibit cell proliferation mediated by an accumulation of cells in the G1 phase and a parallel decrease in the fraction of cells in the S phase [ 14 ], we evaluated whether CM9 changes cyclin E level of Jurkat cells.…”

Section: Resultsmentioning

confidence: 99%

“…In order to search new anticancer agents with a better pharmaco-toxicological profile, we investigated hybrid compounds obtained by inserting ITC group(s) on an NDI scaffold [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we explored the molecular events modulating the previously reported cytotoxic activity of CM9 [ 14 ] and its effects on cell viability when administered together with doxorubicin. CM9 is an asymmetric NDI constituted of two different side chains: One bearing a protonated dimethylaminoethyl side chain deriving from N , N '- bis [3,3'-(dimethylamino)propylamine]-naphthalene-1,4,5,8-tetracarboxylic diimide (N-BDMPrNDI), and the second one characterized by the ITC group ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

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Study of the Cytotoxic Effects of the New Synthetic Isothiocyanate CM9 and Its Fullerene Derivative on Human T-Leukemia Cells

Gianni

Turrini

Milelli

et al. 2015

Toxins

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One important strategy to develop effective anticancer agents is based on natural products. Many active phytochemicals are in human clinical trials and have been used for a long time, alone and in association with conventional anticancer drugs, for the treatment of various types of cancers. A great number of in vitro, in vivo and clinical reports document the multi-target anticancer activities of isothiocyanates and of compounds characterized by a naphthalenetetracarboxylic diimide scaffold. In order to search for new anticancer agents with a better pharmaco-toxicological profile, we investigated hybrid compounds obtained by inserting isothiocyanate group(s) on a naphthalenetetracarboxylic diimide scaffold. Moreover, since water-soluble fullerene derivatives can cross cell membranes thus favoring the delivery of anticancer therapeutics, we explored the cytostatic and cytotoxic activity of hybrid compounds conjugated with fullerene. We studied their cytostatic and cytotoxic effects on a human T-lymphoblastoid cell line by using different flow cytometric assays. In order to better understand their pharmaco-toxicological potential, we also analyzed their genotoxicity. Our global results show that the synthesized compounds reduced significantly the viability of leukemia cells. However, the conjugation with a non-toxic vector did not increase their anticancer potential. This opens an interesting research pattern for certain fullerene properties.

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“…We have previously reported that CM9 caused a strong drop in ΔΨm. That was demonstrated by a number of cells with decreased mitochondrial potential of about 100% [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…In order to search new anticancer agents with a better pharmaco-toxicological profile, we investigated hybrid compounds obtained by inserting ITC group(s) on an NDI scaffold [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Study of the Cytotoxic Effects of the New Synthetic Isothiocyanate CM9 and Its Fullerene Derivative on Human T-Leukemia Cells

Gianni

Turrini

Milelli

et al. 2015

Toxins

Self Cite

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“…The synthesis required the reaction of NDA with 1 M phosphoric acid heated to 100 °C for 27 h under stirring to afford a monoimide dicarboxylic acid in 46% yield, followed by the reaction with one equivalent of ethanolamine at 135 °C for 23 h to afford the desired non‐symmetrical NDI in 72% yield (Figure b) . The synthesis of other non‐symmetrical NDIs bearing isothiocyanate groups as antiproliferative agents has been also reported, and more recently, another analog containing two side chains, namely a dimethylaminoethyl group and an ethylisothiocyanate chain via a 3‐step synthesis in 7% overall yield (Figure c) …”

Section: Introductionmentioning

confidence: 99%

An Efficient Method for the Synthesis of New Non‐Symmetrical Naphthalenediimides

et al. 2018

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Herein we report an efficient synthesis of a series of nonsymmetrical naphthalenediimides (NDIs) bearing different neutral, electron-donating and electron-withdrawing groups in the imide moieties. The success of this method is based in the regioselective synthesis and isolation of pure carbamoyl naphthoic anhydride acid intermediates (CNA) in good yields (54 to 99%) and high purity, from the reaction of naphthalenetetracarboxylic dianhydride acid (NDA) with one equivalent of different primary amines and THF as solvent. The CNA intermediates were refluxed in toluene and gave the naphthalenemonoimides (NMI) in 55 to 89% yields and high purity. The N-benzyl NMI was used as starting material in the synthesis of non-symmetrical NDIs (1 a-m) in 27 to 80% yield with several amines bearing different substituted benzylic groups. In addition, this methodology was extended to obtain other new NDIs (1 n-r) in good yields (67-90%) and purity.

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Diazapyrenes: interaction with nucleic acids and biological activity

Zhirov

Kovalev

Ulshina

et al. 2020

Chem Heterocycl Comp

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DNA is the pharmacological target for many drugs or compounds currently undergoing clinical trials. 1 Developing new drugs and improving the effects of existing drugs is a complex task that goes beyond improving the specificity of a drug with respect to its biological target. Since in many cases only a small fraction of the administered drug compound reaches the pharmacological target, it is necessary to develop strategies for increasing the accumulation of the drug near cellular DNA. The drug delivery strategy should be aimed at increasing circulation time, enhancing tissue-specific accumulation, increasing the efficiency of cellular and nuclear uptake in addition to high specificity and affinity to DNA. The complexity of biological systems makes it difficult to simultaneously incorporate all of these factors into a single drug development algorithm. However, focusing on specificity is relatively simple because the structure of DNA is well known. 2 Currently, there are many strategies of exploiting the known DNA structure for specific binding of drug compounds. One approach is to use small molecules that can recognize nucleic acids and bind to specific areas of DNA, major or minor grooves, or integrate between DNA bases arranged in specific nucleotide sequences. One of the well-studied DNA targets of drugs is the G-quadruplexes (G4). 3 G4 are secondary nucleic acid structures that can form in single-stranded guanine-rich sequences under physiological conditions. 4 Four guanines are paired via hydrogen bonds to form G-quadruplexes. These structures are further stabilized in the presence of metal ions such as potassium ions. Studies of their stability showed that these noncanonical secondary DNA structures are capable of destabilizing the double helix, since many G4 structures are thermodynamically more stable than double-stranded DNA (dsDNA), and their denaturation rate is significantly lower. 5 G4 sequences in eukaryotes play key regulatory functions, including transcriptional regulation of promoters 5b and gene enhancers, 5b,6 translation, 5b,6,7 epigenetic regulation of chromatin 8 and DNA recombination. 5b,8

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Design, synthesis and biological evaluation of new naphtalene diimides bearing isothiocyanate functionality

Cited by 15 publications

References 38 publications

Study of the Cytotoxic Effects of the New Synthetic Isothiocyanate CM9 and Its Fullerene Derivative on Human T-Leukemia Cells

Study of the Cytotoxic Effects of the New Synthetic Isothiocyanate CM9 and Its Fullerene Derivative on Human T-Leukemia Cells

An Efficient Method for the Synthesis of New Non‐Symmetrical Naphthalenediimides

Diazapyrenes: interaction with nucleic acids and biological activity

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