Synthesis, DNA-binding properties, and antitumor activity of novel distamycin derivatives

Arcamone, Federico; Animati, Fabio; Barbieri, B; Configliacchi, Emanuela; D’Alessio, Roberto; Geroni, Cristina; Giuliani, F; Lazzari, Ettore; Menozzi, Milena

doi:10.1021/jm00124a008

Cited by 136 publications

(83 citation statements)

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“…This was found both for DX, which intercalates into DNA (Arcamone et al, 1989), and for VP-16, which does not bind significantly to DNA. The reason for the loss of effect of the DNA topoisomerase II inhibitor is unclear.…”

Section: Discussionmentioning

confidence: 89%

“…To our knowledge, no reports have been published on the influence of polyamine levels on alkylating agents that bind in the DNA minor groove, such as tallimustine and CC-1065 (Hurley et al, 1988;Arcamone et al, 1989). These two drugs bind in the minor groove of AT-rich sequences and alkylate N3 adenine with a high degree of sequence specificity (Broggini et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Treatment with inhibitors of polyamine biosynthesis, which selectively lower intracellular spermine, does not affect the activity of alkylating agents but antagonizes the cytotoxicity of DNA topoisomerase II inhibitors

Desiderio

Bergamaschi²,

Mascellani³

et al. 1997

Br J Cancer

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Summary Inhibitors of ornithine decarboxylase (ODC), such as a-difluoromethylornithine (DFMO), may influence the cytotoxicity of anti-tumour agents that interact with DNA. Intracellular levels of putrescine and spermidine were markedly reduced by ODC inhibitors while the level of spermine, which is the main polyamine in nuclei, was unchanged. By combining a novel inhibitor of ODC, such as (2R, 5R)-6-heptyne-2,5-diamine (MDL 72.175, MAP), with an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), such as 5'-{[(Z)-4-aminobut-2-enyl]methylamino}-5'-deoxyadenosine (MDL 73.81 1, AbeAdo), spermine was selectively depleted in a human ovarian cancer cell line OVCAR-3 (i.e. spermine became almost undetectable whereas the levels of spermidine and putrescine were not affected). The . The addition of spermine before drug treatment restored the sensitivity to the DNA topoisomerase 11 inhibitors, thus indicating that the reduced effect was related to the intracellular spermine level. The reason for the reduction in cytotoxicity is unclear, but it does not appear to be related to a cell cycle effect or to a decrease in the intracellular level of DNA topoisomerase 11. Drugs that modify polyamine biosynthesis are under early clinical development as potential new anti-tumour agents. These findings illustrate the need for caution in combining such drugs with DNA topoisomerase 11 inhibitors.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Treatment with inhibitors of polyamine biosynthesis, which selectively lower intracellular spermine, does not affect the activity of alkylating agents but antagonizes the cytotoxicity of DNA topoisomerase II inhibitors

Desiderio

Bergamaschi²,

Mascellani³

et al. 1997

Br J Cancer

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“…In the search for more ecacious and less toxic drugs, Zugmaier and colleagues (Zugmaier et al, 1992) found that the suramin-analogue heparinoid sodium-pentosan polysulphate (Figure 1), as well as other polyanionic sugars, was able to block the paracrine stimulant eects of GFs released from tumour cells including lung cancer. More recently, a series of polyanionic naphthalene sulphonate derivatives of distamycin A (Arcamone et al, 1989), have been synthesized (Biasoli et al, 1993). These compounds have a common skeleton of four methyl-pyrrolic rings on the naphthalene ring, but vary in the number and position of the SO 3 groups.…”

Section: Introductionmentioning

confidence: 99%

Anti‐insulin‐like growth factor‐I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines

Cupis

Ciomei

Pirani

et al. 1997

British J Pharmacology

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1 The purpose of this study was to investigate the antiproliferative eect and the modulation of the mitogenic insulin-like growth factor-I (IGF-I) system by FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative compounds, on two human non-small cell lung cancer (N-SCLC) cell lines. 2 For cell growth studies the colorimetric MTT and the thymidine incorporation assays were performed; the presence of IGF-I and IGF-binding proteins in conditioned media was revealed by radioimmunoassay and Western ligand blot, respectively. Variations at the IGF-I-receptor level were tested by binding studies on cell monolayers. 3 A signi®cant concentration-and time-dependent cytostatic activity of FCE 26644 (IC 50 &200 mg ml 71 at 72 h) compared to its analogue FCE 27784 (IC 50 4800 mg ml 71) was observed in both cell lines studied. The IGF-I-stimulated proliferation of the IGF-I-responsive A549 cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF-I-like material and reduced the IGF-I binding (IC 50 4100 mg ml 71 ) in both A549 and Ca-Lu-1 cell lines. FCE 26644 (100 mg ml 71 ) did not aect the K D (&0.5 nM) but reduced the B max and the number of receptor sites (50%). 4 Our ®ndings demonstrate that the ability to down-regulate the cell proliferation of N-SCLC cell lines, shown by FCE 26644, depends at least partially, on interference with the`IGF-I mitogenic system'.

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“…Summary Human colon adenocarcinoma cells (LoVo) (Arcamone et al, 1989;Kopka et al, 1985), is a novel antitumour compound currently being investigated in phase I clinical trials ( Figure 1). …”

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confidence: 99%

Characterisation of a LoVo subline resistant to a benzoyl mustard derivative of distamycin A (FCE 24517)

Capolongo¹,

Melegaro²,

Broggini³

et al. 1993

Br J Cancer

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Human colon adenocarcinoma cells (LoVo) resistant to the new antitumor agent FCE 24517 [benzoyl-mustard derivative of distamycin A] (LoVo/24517) are resistant to the selecting agent and related molecules as well as to vinblastine, with marginal or no resistance to other antitumour drugs. Treatment with verapamil, tamoxifen, nicergoline or cyclosporin A only partially restores the activity of FCE 24517 against LoVo/24517 cells. Such results suggest that resistance mechanisms possible specific for this class of compounds are operating. Images Figure 2

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Synthesis, DNA-binding properties, and antitumor activity of novel distamycin derivatives

Cited by 136 publications

References 0 publications

Treatment with inhibitors of polyamine biosynthesis, which selectively lower intracellular spermine, does not affect the activity of alkylating agents but antagonizes the cytotoxicity of DNA topoisomerase II inhibitors

Treatment with inhibitors of polyamine biosynthesis, which selectively lower intracellular spermine, does not affect the activity of alkylating agents but antagonizes the cytotoxicity of DNA topoisomerase II inhibitors

Anti‐insulin‐like growth factor‐I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines

Characterisation of a LoVo subline resistant to a benzoyl mustard derivative of distamycin A (FCE 24517)

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