DNA damage and cytotoxcity induced in mammalian cells by a tetramethylfuroquinolinone derivative

Marzano, Cristina; Severin, Emilia; Pani, B.; Guiotto, A.; Bordin, F.

doi:10.1002/(sici)1098-2280(1997)29:3<256::aid-em5>3.0.co;2-a

Cited by 10 publications

(8 citation statements)

References 18 publications

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“…A small number of publications indicated that α-heterocyclic TSCs and their Cu(II) complexes were capable of in vivo and in vitro inhibition of Topo II at IC 50 below that of the widely employed Topo II poison VP-16 ,, (see section ). Despite these encouraging results, little has been reported on the role that metalation played in the ability of TSCs to inhibit Topo II.…”

Section: Mechanistic Approaches and Proposed Biological Targetsmentioning

confidence: 99%

“…Quinolinone derivatives have been reported to possess pro-apoptotic characteristics, and many quinolinone-, quinoline- and coumarin-based compounds have been shown to be potent Topo II inhibitors . Recently, a series of novel quinolinone Schiff bases and their corresponding copper(II) complexes were tested for their Topo II inhibitory potential and anticancer activity against HepG2 cells.…”

Section: Mechanistic Approaches and Proposed Biological Targetsmentioning

confidence: 99%

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Advances in Copper Complexes as Anticancer Agents

et al. 2013

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Copper is a transition metal that can exist in oxidized (Cu(II)) and reduced (Cu(I)) states. This allows it to participate in redox and catalytic chemistry, making it a suitable cofactor for a diverse range of enzymes and molecules. Copper complexes have been investigated for their therapeutic or diagnostic potential showing effectiveness in cancer treatment due to their cytotoxic action on tumour cells. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of complexes. Up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. The current overview, collecting the most significant strategies adopted in the last four years to design promising anticancer copper(I,II) compounds, aims to provide a useful reference for researchers working in this field

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Section: Mechanistic Approaches and Proposed Biological Targetsmentioning

confidence: 99%

Section: Mechanistic Approaches and Proposed Biological Targetsmentioning

confidence: 99%

Advances in Copper Complexes as Anticancer Agents

et al. 2013

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“…FQ is a furocoumarin isoster having relatively low toxicity [13] and endowed with high antiproliferative activity after UVA irradiation and also in the dark [12]. Therefore its disposition in mice was studied under different experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

“…1). Differently from 8-MOP, this compound shows cytotoxic activity also in the dark without significant genotoxicity [12]. Following irradiation, the angular molecular structure prevents the formation of inter-strand cross-links, a typical lesion induced by 8-MOP.…”

Section: Introductionmentioning

confidence: 97%

Disposition of 1,4,6,8-Tetramethyl-furoquinolinone in Normal and Ascitic Tumor Bearing Mice

Bevilacqua

Baccichetti

Gaion

et al. 2011

Arzneimittelforschung

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1,4,6,8-Tetramethyl-2H-furo[2,3h]quinolin-2-one (FQ) belongs to a series of furocoumarin isosters, designed to obtain new drugs for photochemotherapy. The objective of this study was to characterize the disposition of orally administered 3H-FQ in normal and ascitic tumor bearing mice and to evaluate the influence of UVA irradiation in control mice. This compound was rapidly absorbed and its decay in serum was biphasic. Binding to serum proteins, which was maximum at 30 min (74 %), time-dependently declined. FQ was distributed to all the studied tissues, primarily to the liver and kidneys. The administered radioactivity was excreted mostly in the urine (43 %) and was associated with polar metabolites. The unchanged compound was not present to any detectable extent in the urine. Elimination in the faeces, that may include FQ not absorbed, was low (14 % of administered radioactivity), emphasizing the quantitatively efficient gastrointestinal absorption of the drug. UVA irradiation of FQ-treated mice for 2 h caused a significant increase in radioactivity measured in serum as well as in the liver. In mice bearing Ehrlich ascitic tumor, serum and tissue concentrations were lower than in control animals, possibly due to the larger volume of body fluids (10+/-4 ml of ascitic fluid) available for drug distribution.

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“…More recently, to develop new derivatives with better features than &MOP, various authors have focused on the insertion of a heteroatom into the furocoumarin skeleton, thus obtaining furocoumarin isosters, such as, for example, some azapsoralens (13)(14)(15) and various sulfur and selenium derivatives (1619). Angelicin isosters were also studied, in particular, some methylfuroquinolinones, in which a nitrogen atom replaces the oxygen at the pyronic ring (20)(21)(22). In addition some 4-amino-3-chloroangelicin derivatives carrying a sulfur atom substituting for the oxygen at the furan ring were also prepared (23).…”

Section: Introductionmentioning

confidence: 99%

Photobiological Properties of 1′‐Thieno‐4,6,4′‐trimethylangelicin

Bordin

Marzano

Baccichetti

et al. 1998

Photochem & Photobiology

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Some photobiological properties of 1'-thieno-4,6,4'-trimethylangelicin (TTMA), a new isoster of 4,6,4'-trimethylangelicin (TMA) were studied in comparison with the parent compound. The TTMA absorbs UVA light and photobinds in vitro to DNA more efficiently than TMA; however, in Ehrlich cells in vivo TTMA linked to DNA to a lesser extent than the parent compound. In general, the formation of damage into DNA is in line with this last result: In fact, TTMA and TMA form equivalent amounts of interstrand cross-links (ISC) both in vitro in linearized PM2 DNA and in vivo in HeLa cells. In this system TTMA induces DNA-protein cross-links (DPC) more efficiently than TMA; on the contrary, no significant amounts of single-strand breaks were detected with both compounds. The antiproliferative activity of TTMA is consistent with these results, being only slightly more pronounced than that of TMA. Experiments carried out using double irradiation demonstrated that these drugs are capable of inducing antiproliferative effects by biphotonic reactions, including the formation of both ISC and DPC. Thus, replacement of the oxygen atom by a sulfur increases the UV absorption of the drug and its capacity to photobind to DNA in vitro but does not yield a comparable enhancement of its photosensitizing properties in vivo; this might be due to various reasons, for instance to an increase in the lipophilic character that could modify the behavior in vivo.

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DNA damage and cytotoxcity induced in mammalian cells by a tetramethylfuroquinolinone derivative

Cited by 10 publications

References 18 publications

Advances in Copper Complexes as Anticancer Agents

Advances in Copper Complexes as Anticancer Agents

Disposition of 1,4,6,8-Tetramethyl-furoquinolinone in Normal and Ascitic Tumor Bearing Mice

Photobiological Properties of 1′‐Thieno‐4,6,4′‐trimethylangelicin

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