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distamycin/neoplasms
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Synthesis of hybrid distamycin-cysteine labeled with 99mTc: a model for a novel class of cancer imaging agents.
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The synthesis of a hybrid constituted by distamycin A and cysteine labeled with the gamma-emitting radionuclide 99mTc to afford the conjugate complex 5 is reported. This new radiopharmaceutical is of potential interest as tumor imaging agent in diagnostic nuclear medicine. The preparation of the
Distamycin-A derivatives potentiate tumor-necrosis-factor activity via the modulation of tyrosine phosphorylation.
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The cytotoxic activities of 2 novel distamycin-A derivatives, FCE 24517 and FCE 25450A, alone and in combination with tumor-necrosis factor-alpha (TNF), were studied. Both drugs, especially FCE 25450A, analyzed extensively here, inhibited the growth of HL60 promyelocytic cells, and human SV80 and
Inhibition of telomerase activity by a distamycin derivative: effects on cell proliferation and induction of apoptosis in human cancer cells.
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In this study, we evaluated the potential of the distamycin derivative MEN 10716 as a telomerase inhibitor. Exposure of human melanoma cell extracts to MEN 10716 induced a dose-dependent inhibition of telomerase activity, with an IC50 of 24+/-3 microM. When intact JR8 melanoma cells were chronically
The anti-cancer agent distamycin A displaces essential transcription factors and selectively inhibits myogenic differentiation.
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The anticancer drug, distamycin A, alters DNA conformation by binding to A/T-rich domains. We propose that binding of the drug to DNA alters transcription factor interactions and that this may alter genetic regulation. We have analyzed the effects of distamycin A upon expression of the
Inhibition of growth factor mitogenicity and growth of tumor cell xenografts by a sulfonated distamycin A derivative.
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Interference with growth factor-receptor interactions may have particular relevance in efforts to intervene clinically in both autocrine and paracrine aspects of malignancy. Suramin is a synthetic anticancer agent that works, in part, by blocking the binding of growth factors to their receptors.
Endothelial cells overexpressing basic fibroblast growth factor (FGF-2) induce vascular tumors in immunodeficient mice.
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Basic fibroblast growth factor (FGF-2) is expressed in vascular endothelium during tumor neovascularization and angioproliferative diseases, including vascular tumors and Kaposi's sarcoma (KS). We have investigated the in vivo biological consequences of endothelial cell activation by endogenous
Antiangiogenic, antitumoural and antimetastatic effects of two distamycin A derivatives with anti-HIV-1 Tat activity in a Kaposi's sarcoma-like murine model.
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The antiangiogenic, antitumoural and antimetastatic effects of two novel sulphonic derivatives of distamycin A, PNU145156E and PNU153429, were studied in a Kaposi's sarcoma-like tumour model obtained by injecting nude mice with cells releasing extracellular HIV-Tat protein, derived from a tumour
A phase I and pharmacokinetic study of tallimustine [PNU 152241 (FCE 24517)] in patients with advanced cancer.
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Tallimustine [PNU 152241 (FCE 24517)] is a synthetic derivative of the DNA minor groove binder distamycin A, in which the NH2-terminal formyl group is substituted by benzoyl mustard. In this Phase I clinical trial, patients with advanced solid tumors received i.v. bolus injections of tallimustine
Cytotoxic and antitumor activity of MEN 10710, a novel alkylating derivative of distamycin.
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MEN 10710 is a new synthetic distamycin derivative possessing four pyrrole rings and a bis-(2-chloroethyl)aminophenyl moiety linked to the oligopyrrole backbone by a flexible butanamido chain. Its biological properties have been investigated in comparison with the structurally related compound,
Cytotoxics derived from distamycin A and congeners.
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Distamycin A is an antibiotic, characterised by an oligopeptidic pyrrolocarbamoyl frame ending with an amidino moiety, which binds reversibly to DNA minor groove with high selectivity for TA-rich sequences and shows antiviral and antiprotozoal activity. Distamycin was used as DNA sequence selective
In vitro cytotoxicity of GC sequence directed alkylating agents related to distamycin.
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Imidazole containing analogues 7, 10, and 17 of distamycin wherein the C-terminus contain a dimethylamino moiety have been shown to selectively bind to the minor groove of GC-rich sequences. Accordingly, these agents were employed as vectors for the delivery of a variety of alkylating agents to
Synthesis and biological evaluation of distamycin analogues - new potential anticancer agents.
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Eight of analogues of distamycin, potential minor-groove binders, were synthesized and tested for in-vitro cytotoxicity towards human breast cancer cells MCF-7 and MDA-MB-231. The method of synthesis is simple and convenient. All of the compounds 1-8 showed antiproliferative and cytotoxic effects
Distamycin inhibits the binding of a nuclear factor to the -278/-256 upstream sequence of the human HLA-DR alpha gene.
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In this study we analyse the effects of the anti-tumor compound distamycin on the binding of nuclear factor(s) to a synthetic oligonucleotide (GTATA/IFN-gamma) mimicking a putative regulatory region of the human HLA-DR alpha gene. This region contains the sequence (GTATA), that is required for
Novel linked antiviral and antitumor agents related to netropsin and distamycin: synthesis and biological evaluation.
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A group of oligopeptides have been synthesized which are structurally related to the natural antiviral antitumor antibiotics netropsin and distamycin bearing two such moieties linked by polymethylene bridges. Cytostatic activity against both human and murine tumor cell lines and their in vitro
Sequence-specific recognition of the HIV-1 long terminal repeat by distamycin: a DNAase I footprinting study.
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Pharmacological modulation of the interaction between transcription factors and target DNA sequences of cellular and viral genes could have important effects in the experimental therapy of a large variety of human pathologies. For instance, alteration of the DNA/protein interaction might be among
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