Novel 3,6-bis(imidazolidine)acridines as effective photosensitizers for photodynamic therapy.


:The photoeffect of new proflavine derivatives with DNA-binding and antitumour activities, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides (AcrDIMs), was studied to evaluate them as potential photosensitizers for photodynamic antitumor therapy. EPR measurements showed that superoxide radical anion and singlet oxygen were produced upon irradiation of AcrDIMs with UV-A light (>300nm) in the presence of molecular oxygen. This indicates that AcrDIMs may act as photosensitizers. The most active pentyl-AcrDIM and hexyl-AcrDIM displayed photocytotoxic effect toward the mouse lymphocytic leukemia cell line L1210 and human ovarian cancer cells A2780. Antitumor activity of pentyl-AcrDIM increased as high as about 12 times (72h incubation) after irradiation of A2780 cells (365nm, 1.05J/cm(2)). The photocytotoxicity seems to be associated with oxidative stress. Concerning the cell cycle, flow cytometry showed an arrest in the S-phase already 4h after irradiation. In a comet assay, no genotoxicity of AcrDIMs was found. Typical morphologic changes and formation of DNA-ladders indicated induction of apoptotic cell death, though no activation of caspase-3 was observed. Investigation of intracellular localization of pentyl-AcrDIM confirmed its partial accumulation in mitochondria and lysosomes. After irradiation of the A2780 cells, colocalization of pentyl-AcrDIM with monodansylcadaverine, a lysosomal dye, was proven, suggesting that lysosomes in the irradiated cells may be involved in the cell death.


Bioorg Med Chem


Cižeková L,Grolmusová A,Ipóthová Z,Barbieriková Z,Brezová V,Hunáková L,Imrich J,Janovec L,Dovinová I,Paulíková H




Has Abstract


2014-09-01 00:00:00














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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    更新日期:2005-10-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Zhang H,Tong R,Bai L,Shi J,Ouyang L

    更新日期:2016-04-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Vasilakaki S,Barbayianni E,Leonis G,Papadopoulos MG,Mavromoustakos T,Gelb MH,Kokotos G

    更新日期:2016-04-15 00:00:00

  • Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ishida J,Yamamoto H,Kido Y,Kamijo K,Murano K,Miyake H,Ohkubo M,Kinoshita T,Warizaya M,Iwashita A,Mihara K,Matsuoka N,Hattori K

    更新日期:2006-03-01 00:00:00

  • Comparative reactivity analysis of small-molecule thiol surrogates.

    abstract::Targeted covalent inhibitors represent an increasingly popular approach to modulate challenging drug targets. Since covalent and non-covalent interactions are both contributing to the affinity of these compounds, evaluation of their reactivity is a key-step to find feasible warheads. There are well-established HPLC- a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Petri L,Ábrányi-Balogh P,Varga PR,Imre T,Keserű GM

    更新日期:2020-04-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Akamatsu M,Fujimoto Y,Kataoka M,Suda Y,Kusumoto S,Fukase K

    更新日期:2006-10-01 00:00:00

  • Branched-chain and unsaturated 1,7-diaminoheptane derivatives as deoxyhypusine synthase inhibitors.

    abstract::Deoxyhypusine synthase catalyzes the first step in the posttranslational biosynthesis of the unusual amino acid hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine] in eukaryotic translation initiation factor 5A (eIF-5A). eIF-5A and its single hypusine residue are essential for cell proliferation. Two series of 1,7-dia...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lee YB,Folk JE

    更新日期:1998-03-01 00:00:00