114459-62-0Relevant articles and documents
Homologation of polyamines in the rapid synthesis of lipospermine conjugates and related lipoplexes
Geall, Andrew J.,Blagbrough, Ian S.
, p. 2449 - 2460 (2000)
Lipopolyamine amides are useful cationic lipids, synthetic vectors for non-viral gene delivery. Desymmetrisation of readily available symmetrical polyamines is an important first step in the synthesis of such compounds. The application of trifluoroacetyl
DNA condensation by cholesterol polyamine carbamates: A first step in gene therapy
Geall, Andrew J.,Blagbrough, Ian S.
, p. 145 - 150 (1999)
Novel cholesterol polyamine carbamates were prepared and their pKa values determined potentiometrically. Using the Henderson-Hasselbach equation, their charge, at physiological pH, was determined. Binding affinity for calf thymus DNA was measured using an
Evaluation method for polyamine uptake by N1-Dansylspermine
Takao, Koichi,Sugita, Yoshiaki,Shirahata, Akira
, p. 533 - 539 (2010)
Polyamine uptake by the polyamine transport system (PTS) in HTC cells was studied without the use of radioisotope-labeled polyamines. N-Dansylspermine (DNS343) was selected as a candidate probe to examine the PTS. DNS343 was incorporated into HTC cells, and its distribution in the cells was confirmed by fluorescence microscopy. The incorporation of DNS343 via PTS was confirmed by a competition study with bis(3-aminopropyl)amine, which is incorporated into cells via the PTS. In addition, the temperature dependency of DNS343 uptake and studies with inhibitors of ornithine decarboxylase and proteoglycan synthesis supported the use of DNS 343 as a fluorescent probe for the PTS. The kinetics studies for HTC cells treated with or without an ornithine decarboxylase inhibitor indicated that DNS343 uptake was saturable and that the apparent Km values for the PTS were approximately 1.5 μM in both types of cells at 37°C. Thus, we developed an assay method for the PTS by high-performance liquid-chromatography with DNS343. The inhibitory effect of polyamine analogs and related compounds on DNS343 uptake was then examined and discussed. Springer-Verlag 2009.
Structure-activity relationships of lipopolysaccharide sequestration in N-alkylpolyamines
Shrestha, Anurupa,Sil, Diptesh,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,David, Sunil A.
, p. 2478 - 2481 (2009)
We have previously shown that simple N-acyl or N-alkyl polyamines bind to and sequester Gram-negative bacterial lipopolysaccharide, affording protection against lethality in animal models of endotoxicosis. Several iterative design-and-test cycles of SAR studies, including high-throughput screens, had converged on compounds with polyamine scaffolds which have been investigated extensively with reference to the number, position, and length of acyl or alkyl appendages. However, the polyamine backbone itself had not been explored sufficiently, and it was not known if incremental variations on the polymethylene spacing would affect LPS-binding and neutralization properties. We have now systematically explored the relationship between variously elongated spermidine [NH2-(CH2)3-NH-(CH2) 4-NH2] and norspermidine [NH2-(CH2)3-NH-(CH2) 3-NH2] backbones, with the N-alkyl group being held constant at C16 in order to examine if changing the spacing between the inner secondary amines may yield additional SAR information. We find that the norspermine-type compounds consistently showed higher activity compared to corresponding spermine homologues.
Synthesis of cholesterol-polyamine carbamates: PKa studies and condensation of calf thymus DNA
Geall, Andrew J.,Taylor, Richard J.,Earll, Mark E.,Eaton, Michael A. W.,Blagbrough, Ian S.
, p. 1403 - 1404 (1998)
Novel cholesterol-polyamine carbamates have been prepared and their pKas determined potentiometrically for conjugates substituted with up to five amino functional groups and the binding affinity for calf thymus DNA has also been determined; these polyamine carbamates are models for lipoplex formation with respect to gene delivery (lipofection), a key first step in gene therapy.
Synthesis and cellular studies of polyamine conjugates of a mercaptomethyl-carboranylporphyrin
Bhupathiraju, N.V.S. Dinesh K.,Vicente, M. Graca H.
, p. 485 - 495 (2013)
Seven polyamine conjugates of a tri(p-carboranylmethylthio) tetrafluorophenylporphyrin were prepared in high yields by sequential substitution of the p-phenyl fluoride of tetrakis(pentafluorophenyl)porphyrin (TPPF), and investigated as boron delivery agen
Novel Polyamine-Naphthalene Diimide Conjugates Targeting Histone Deacetylases and DNA for Cancer Phenotype Reprogramming
Pasini, Alice,Marchetti, Chiara,Sissi, Claudia,Cortesi, Marilisa,Giordano, Emanuele,Minarini, Anna,Milelli, Andrea
, p. 1218 - 1223 (2017)
A series of hybrid compounds was designed to target histone deacetylases and ds-/G-quadruplex DNAs by merging structural features deriving from Scriptaid and compound 1. Compound 6 binds different DNA arrangements, inhibits HDACs both in vitro and in cells, and is able to induce a reduction of cell proliferation. Moreover, compound 6 displays cell phenotype-reprogramming properties since it prevents the epithelial to mesenchymal transition in cancer cells, inducing a less aggressive and migratory phenotype, which is one of the goals of present innovative strategies in cancer therapies.
DNA condensation by bile acid conjugates of thermine and spermine
Blagbrough, Ian S.,Al-Hadithi, Dima,Geall, Andrew J.
, p. 139 - 144 (1999)
DNA condensation was achieved with polyamine conjugates of bile acids. Spermine and thermine, linear tetraamines, were mono-acylated on a primary amine with cholic and lithocholic acids. The resulting polyamine amides were triamines containing either a propyl-butyl or a dipropyl spacing. Thus, the former mimics both the positive charge and its regiochemical distribution found in the natural product spermidine. Calf thymus DNA was extended by saturation with an intercalator, ethidium bromide. DNA binding affinity was then measured by fluorescence quenching with detection of residual intercalated ethidium bromide at 600 nm. The results obtained with this exclusion assay show that polyamine lithocholic acid conjugates condense DNA more efficiently than the analogous cholic acid polyamine amides.
A spermine-conjugated lipophilic Pt(iv) prodrug designed to eliminate cancer stem cells in ovarian cancer
Stilgenbauer, Morgan,Jayawardhana, Amarasooriya M. D. S.,Datta, Payel,Yue, Zhizhou,Gray, Michael,Nielsen, Frederick,Bowers, David J.,Xiao, Haihua,Zheng, Yao-Rong
, p. 6106 - 6109 (2019)
We developed a spermine-conjugated lipophilic Pt(iv) prodrug that is able to reduce the cancer stem cell population in ovarian cancer. The therapeutic effect is attributed to the hydrophobic tail and cationic spermine head group, the combination of which allows the Pt(iv) prodrug to localize in mitochondria and induce corresponding damage.
Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: Design, synthesis, and validation
Corcé, Vincent,Morin, Emmanuelle,Guihéneuf, Solène,Renault, Eric,Renaud, Stéphanie,Cannie, Isabelle,Tripier, Rapha?l,Lima, Luís M. P.,Julienne, Karine,Gouin, Sébastien G.,Loréal, Olivier,Deniaud, David,Gaboriau, Fran?ois
, p. 1952 - 1968 (2012)
Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μ. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.
Serum Compatible Spermine-Based Cationic Lipids with Nonidentical Hydrocarbon Tails Mediate High Transfection Efficiency
Thongbamrer, Chopaka,Roobsoong, Wanlapa,Sattabongkot, Jetsumon,Opanasopit, Praneet,Yingyongnarongkul, Boon-ek
, (2022/02/03)
Cationic lipids are widely used as nonviral synthetic vectors for gene delivery as a safer alternative to viral vectors. In this work, a library of L-shaped spermine-based cationic lipids with identical and nonidentical hydrophobic chains having variable carbon lengths (from C10 to C18) was designed and synthesized. These lipids were characterized and the structure-activity relationships of these compounds were determined for DNA binding and transfection ability when formulated as cationic liposomes. The liposomes were then used successfully for the transfection of HEK293T, HeLa, PC3, H460, HepG2, SH-SY5Y and Calu’3 cell lines. The transfection efficiency of lipids with nonidentical hydrocarbon chains was greater than the identical analogue. These reagents exhibited superior efficiency to the commercial reagent, Lipofectamine3000, under both serum-free and 10–40 % serum conditions in HEK293T, HeLa and H460 cell lines. The lipids were not toxic to the tested cell line. The results suggest that L-shaped spermine-based cationic lipids with nonidentical hydrocarbon tails could serve as efficient and safe nonviral vector gene carriers in further in vivo studies.
Improved synthesis of the bifunctional chelator p-SCN-Bn-HOPO
Bhupathiraju, N.V.S. Dinesh K.,Younes, Ali,Cao, Minhua,Ali, Jafar,Cicek, Huseyin T.,Tully, Kathryn M.,Ponnala, Shashikanth,Babich, John W.,Deri, Melissa A.,Lewis, Jason S.,Francesconi, Lynn C.,Drain, Charles Michael
, p. 6866 - 6871 (2019/07/22)
The bifunctional ligand p-SCN-Bn-HOPO, which has four 1,2-hydroxypyridinone groups on a spermine backbone with an isothiocyanate linker, has been shown to be an efficient and stable chelator for Zr(iv) and, more importantly, the radioisotope 89Zr for use in radiolabeling antibodies for positron emission tomography (PET) imaging. Previous studies of 89Zr-HOPO-trastuzumab in mice showed low background, good tumor to organ contrast, and very low bone uptake which show p-SCN-Bn-HOPO to be an important next-generation bifunctional chelator for radioimmunoPET imaging with 89Zr. However, the reported synthesis of p-SCN-Bn-HOPO involves nine steps and multiple HPLC purifications with an overall yield of about 1.4%. Herein we report an improved and efficient synthesis of p-SCN-Bn-HOPO in four steps with 14.3% overall yield which will improve its availability for further biological studies and wider application in PET imaging. The new synthetic route also allows variation in linker length and chemistries which may be helpful in modifying in vivo clearance behaviors of future agents.
