Regioselective binding of spermine, N¹,N12-bismethylspermine, and N¹,N12-bisethylspermine to tRNA Phe as revealed by 750 MHz ¹H-NMR and its possible correlation with cell cycling and cytotoxicity

Frydman, Benjamiǹ; Westler, William M.; Valasinas, Aldonia; Kramer, Debora L.; Porter, Carl W.

doi:10.1590/s0103-50531999000400014

Cited by 5 publications

(1 citation statement)

References 15 publications

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“…Binding of these compounds to DNA and chromatin (4,12), tRNA (15)(16)(17), and RNA (5) results from electrostatic forces as well as from hydrogenbonding interactions that arise from the protonated secondary nitrogens on the polyamines and acceptor residues on the nucleic acids. The binding of synthetic polyamine analogues to nucleic acids provides the most likely explanation for their strong antiproliferative effects (14,24) since the structural distortions that they introduce in nucleic acids impair the latter's biological functions (12).…”

Section: Discussionmentioning

confidence: 99%

Novel Synthetic Polyamines Are Effective in the Treatment of Experimental Microsporidiosis, an Opportunistic AIDS-Associated Infection

Bacchi

Weiss

Lane

et al. 2002

Antimicrob Agents Chemother

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Microsporidia are eukaryotic obligate intracellular protists that are emerging pathogens in immunocompromised hosts, such as patients with AIDS or patients who have undergone organ transplantation. We have demonstrated in vitro and in vivo that synthetic polyamine analogs are effective antimicrosporidial agents with a broad therapeutic window. CD8-knockout mice or nude mice infected with the microsporidian Encephalitozoon cuniculi were cured when they were treated with four different novel polyamine analogs at doses ranging from 1.25 to 5 mg/kg of body weight/day for a total of 10 days. Cured animals demonstrated no evidence of parasitemia by either PCR or histologic staining of tissues 30 days after untreated control animals died.

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Section: Discussionmentioning

confidence: 99%

Novel Synthetic Polyamines Are Effective in the Treatment of Experimental Microsporidiosis, an Opportunistic AIDS-Associated Infection

Bacchi

Weiss

Lane

et al. 2002

Antimicrob Agents Chemother

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Polyaminooligonucleotide: NMR structure of duplex DNA containing a nucleoside with spermine residue, N-[4,9,13-triazatridecan-1-yl]-2′-deoxycytidine

Brzezinska

Gdaniec

Popenda

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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Cis-Unsaturated Analogues of 3,8,13,18,23-Pentaazapentacosane (BE-4-4-4-4): Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cell Lines

Reddy¹,

Sarkar²,

Valasinas³

et al. 2000

J. Med. Chem.

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From the results of our previous physicochemical studies of polyamine-nucleic acid interactions, we concluded that polyamine analogues in cisoidal conformation are capable of wrapping around the major groove of the double helix, of displacing natural polyamines from their nucleic acid binding sites, and of inhibiting cell division. On the basis of this hypothesis, nine unsaturated pentamines, formally derived from the cytotoxic pentamine 3,8,13,18,23-pentaazapentacosane (BE-4-4-4-4), were prepared in an attempt to increase antineoplastic activity. Cis-double bonds were introduced in all possible sites in the saturated pentaazapentacosane structure of BE-4-4-4-4 to yield two pentacosenes, four pentacosadienes, two pentacosatrienes, and one pentacosatetraene. Cis-double bonds should also provide good targets for mixed-function oxidases that might eliminate the accumulation of unsaturated pentamines in serum, thereby reducing systemic toxicity in animals. We determined the ability of these new pentamines to inhibit growth in four cultured human prostate cancer cell lines (LnCap, DU145, PC-3, and DuPro) using a MTT assay. LnCap and DU145 cells were very sensitive, PC-3 cells were relatively resistant, and DuPro cells were intermediate in sensitivity to most of these synthetic pentamines. In all cell lines, pentamines that had unsaturation(s) at the end of the chain showed the highest cell growth inhibitory effects. The cellular uptake, effects on cellular polyamine levels, and cytotoxicity of these pentamines on one representative prostate cancer cell line (DuPro) were further examined with a colony-forming efficiency (CFE) assay. The pentamines with unsaturation(s) at the end of the chain were once again the most cytotoxic among both the saturated (BE-4-4-4-4) and unsaturated analogues. Appreciable amounts of all pentamines entered DuPro cells and depleted cellular polyamine pools by day 6 of treatment. For most pentamines, however, cell growth inhibitory and cytotoxic effects could not be directly correlated either with their cellular uptake or with their ability to deplete cellular polyamine pools. The position of the double bonds in the aliphatic backbone seems to be the most important determinant of cytotoxicity. For some pentamines, however, depletion of cellular polyamines may add to their efficacy.

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Regioselective binding of spermine, N¹,N12-bismethylspermine, and N¹,N12-bisethylspermine to tRNA Phe as revealed by 750 MHz ¹H-NMR and its possible correlation with cell cycling and cytotoxicity

Cited by 5 publications

References 15 publications

Novel Synthetic Polyamines Are Effective in the Treatment of Experimental Microsporidiosis, an Opportunistic AIDS-Associated Infection

Novel Synthetic Polyamines Are Effective in the Treatment of Experimental Microsporidiosis, an Opportunistic AIDS-Associated Infection

Polyaminooligonucleotide: NMR structure of duplex DNA containing a nucleoside with spermine residue, N-[4,9,13-triazatridecan-1-yl]-2′-deoxycytidine

Cis-Unsaturated Analogues of 3,8,13,18,23-Pentaazapentacosane (BE-4-4-4-4): Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cell Lines

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