68076-36-8Relevant articles and documents
Designing the polyamine pharmacophore: Influence of N-substituents on the transport behavior of polyamine conjugates
Kaur, Navneet,Deleros, Jean-Guy,Archer, Jennifer,Weagraff, Nathan Z.,Martin, Bénédicte,Phanstiel IV, Otto
, p. 2551 - 2560 (2008)
N-Ethylated N-arylmethyl polyamine conjugates were synthesized and evaluated for their ability to target the polyamine transporter (PAT). To understand the effect of N-ethylation upon PAT selectivity, ethyl groups were appended onto a PAT-selective N1-anthracenenylmethyl homospermidine derivative. 1b. Bioevaluation in L1210 murine leukemia cells and in two Chinese hamster ovary cell lines (PAT-active CHO and PAT-deficient CHO-MG) revealed a dramatic decrease in PAT targeting ability upon N1 or N5 ethylation of the pharmacophore 1b. Experiments using the amine oxidase inhibitor, aminoguanidine (AG, 2 mM), revealed that the N9-ethyl and N9-methyl analogues were able to retain their PAT selectivity and cytotoxicity properties in the presence or absence of AG. In contrast, the lead compound 1b (containing a terminal NH2 group) revealed a dramatic reduction in both its PAT-targeting ability and cytotoxicity in the absence of AG. An improved balance between these three properties of PAT-targeting, cytotoxicity and metabolic stability can be attained via N-methylation at the N9-position.
Synthesis and structure-property relationship of polyester-urethanes and their evaluation for the regeneration of contractile tissues
Sartori, Susanna,Boffito, Monica,Serafini, Piero,Caporale, Andrea,Silvestri, Antonella,Bernardi, Ettore,Sassi, Maria Paola,Boccafoschi, Francesca,Ciardelli, Gianluca
, p. 1366 - 1376 (2013)
The structure-property relationship of degradable polyurethanes from non toxic building blocks was studied by synthesising four different biodegradable poly(ester urethanes) from poly(s-caprolactone) (PCL) diol, 1,4- diisocyanatobutane and different chain extenders. For instance, the chain extenders were an amino acid derivative diamine, an amino acid derivative diol, a cyclic diol and a custom made diamine, containing an enzymatically degradable peptide (Ala-Ala sequence). Physicochemical and morphological characterisation (SEC, DSC, DMA, AFM) was performed, showing the influence of the chain extender on the polyurethane properties. A correlation between surface domain morphologies and thermal properties was highlighted and a relationship between the biological response and surface morphologies was observed. Collecting mechanical characterisation and myoblast cell culture results together, the polyurethane synthesised with the amino acid derivative diamine resulted the most promising candidate for fabricating scaffolds supporting the regeneration of muscle tissues.
Ion pairing between the chain ends induces folding of a flexible zwitterion in methanol
Schmuck, Carsten,Dudaczek, Juergen
, p. 3326 - 3330 (2007)
A well defined folded loop structure can be induced in a flexible zwitterion 10 in the polar and protic solvent methanol by charge interactions between the two termini of the zwitterion. In 10 a (guanidiniocarbonyl)pyrrole moiety, a highly efficient oxoan
Potentiation of BCNU cytotoxicity by molecules targeting abasic lesions in DNA
Alarcon, Karine,Demeunynck, Martine,Lhomme, Jean,Carrez, Danièle,Croisy, Alain
, p. 1901 - 1910 (2001)
We describe the synthesis, DNA binding measurements and pharmacological properties of a series of new heterodimeric molecules, in which a 2,6-diaminopurine is linked to a 9-aminoacridine chrimophore. The linking chain contains a central N,N′-disubstituted guanidine, connected to the two chromophores by polymethylenic units of variable length. Copyright
Synthesis and characterization of segmented copoly(ether urea)s with uniform hard segments
Versteegen, Ron M.,Sijbesma, Rint P.,Meijer
, p. 3176 - 3184 (2005)
Employing protective group strategy and novel isocyanate chemistry, segmented copoly-(ether urea)s with uniform hard segments were prepared. Amine-terminated poly(tetrahydrofuran) served as the soft segment of these polymers. The size of the hard segments and the number of urea groups it contains were varied systematically, and their influence on the properties was investigated. The strength of hydrogen bonding between the urea groups in monodisperse hard segments containing exactly 1 to exactly 4 urea groups was studied by infrared spectroscopy and compared with materials containing polydisperse hard segments. The strength of hydrogen bonding in polymers possessing exactly two urea groups per hard segment resulted in an optimal balance between excellent mechanical properties and good processability and solubility.
New methods for side-chain protection of cysteine
West, Christopher W.,Estiarte, M. Angels,Rich, Daniel H.
, p. 1205 - 1208 (2001)
Matrix presented Cysteine sulfhydryl protection with either the Fmoc or the Fm group was accomplished in one step and in high yield using commercially available FmocCl or FmocOSu, respectively. Mechanisms for the Fmoc to Fm transformations are discussed.
ATP13A3 is a major component of the enigmatic mammalian polyamine transport system
Hamouda, Norin Nabil,van den Haute, Chris,Vanhoutte, Roeland,Sannerud, Ragna,Azfar, Mujahid,Mayer, Rupert,Calabuig, álvaro Cortés,Swinnen, Johannes V.,Agostinis, Patrizia,Baekelandt, Veerle,Annaert, Wim,Impens, Francis,Verhelst, Steven H.L.,Eggermont, Jan,Martin, Shaun,Vangheluwe, Peter
, (2021/03/24)
Polyamines, such as putrescine, spermidine, and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor methylglyoxal bis-(guanylhydrazone) (MGBG), but the molecular defects responsible for these cellular characteristics remain unknown. By genome sequencing of CHO-MG cells, we identified mutations in an unexplored gene, ATP13A3, and found disturbed mRNA and protein expression. ATP13A3 encodes for an orphan P5B-ATPase (ATP13A3), a P-type transport ATPase that represents a candidate polyamine transporter. Interestingly, ATP13A3 complemented the putrescine transport deficiency and MGBG resistance of CHO-MG cells, whereas its knockdown in WT cells induced a CHO-MG phenotype demonstrated as a decrease in putrescine uptake and MGBG sensitivity. Taken together, our findings identify ATP13A3, which has been previously genetically linked with pulmonary arterial hypertension, as a major component of the mammalian polyamine transport system that confers sensitivity to MGBG.
Synthesis, electrochemistry, DNA binding and in vitro cytotoxic activity of tripodal ferrocenyl bis-naphthalimide derivatives
Fan, Yan-Ru,Wang, Bo-Jin,Jia, Deng-Guo,Yang, Xin-Bin,Huang, Yu
, (2021/04/15)
A series of tripodal ferrocenyl bis-naphthalimide derivatives were synthesized and characterized. All of the bis-naphthalimide derivatives exhibited good DNA binding ability which was confirmed by ethidium bromide (EB) displacement experiment and ultraviolet (UV)-visible absorption titration. And the binding mode of these compounds was proved to be a hybrid binding mode by experiments. The cytotoxicity of synthesized compounds against 4 different human cancer cell lines (EC109, BGC823, SGC7901 and HEPG2) was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. All of the bis-naphthalimide derivatives exhibited good anticancer activity than the positive control drug (amonafide), which was due to the promotion of reactive oxygen species (ROS) level in test cancer cells by the reversible one-electron redox process of ferrocenyl bis-naphthalimide derivatives. Although there was no obvious relationship between the binding constants and the chain length, the structure cytotoxicity relationship revealed that the linker of n = 3, m = 1 was the best choice for the tested tripodol bis-naphthalimide derivatives. Synopsis: A series of tripodal ferrocenyl bis-naphthalimide derivatives were synthesized to study the DNA binding ability and the cytotoxicity induced by reactive oxygen species. All of the compounds exhibited good DNA binding ability. And the structure cytotoxicity relationship revealed that the structure of 5h was the best choice.