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1.
J Agric Food Chem ; 53(2): 211-5, 2005 Jan 26.
Article in English | MEDLINE | ID: mdl-15656651

ABSTRACT

The paper refers the analytical potentialities of the oxa-azamacrocycles as potentiometric ionophores for the construction of electrodes selective to nitrate. Afterward, the membrane selective to nitrate is designed and optimized using a [3.3.3.3]oxazane as an ionophore. The membrane was prepared using dibutylphthalate as a solvent mediator, tetraoctylammonium as a lipophilic membrane additive, and poly(vinyl chloride (PVC) as a polymeric matrix, applied directly onto a conductive graphite/epoxy resin support. The electrodes presented a slope of 60 +/- 0.1 mV log(-1), a low limit of linear response of 4.2 x 10(-6) mol L(-1), a useful lifetime of 1 year, and improved selectivity characteristics when compared with other nitrate electrodes. The good working characteristics of this electrode, constructed without inner-reference solution, made possible its application to the determination of nitrate in different types of vegetables and bottled mineral waters without the use of a conditioning solution. The application of a significant F test proved that the results obtained were similar to those attained by application of the brucine spectrophotometric method adopted as a reference technique. Linear regression analysis also showed good agreement between the results obtained by the proposed method and the reference one.


Subject(s)
Ion-Selective Electrodes , Nitrates/analysis , Vegetables/chemistry , Water/chemistry , Chlorides , Ionophores , Polyvinyls , Sensitivity and Specificity
2.
Biochem Soc Trans ; 31(2): 407-10, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12653648

ABSTRACT

A number of polyamine derivatives have demonstrated potential as therapeutic agents. For example, 1,12-bisethylspermine and bisnaphthalimide (elinafide) are currently in phase I clinical trials for the treatment of certain cancers. Here, the biological activities of two new groups of polyamine derivative, namely the oxa-polyamines and the bisnaphthalimides, are presented. The most active compounds in the oxa-polyamine and bisnaphthalimido series possessed IC(50) values of 2.93 and 1.38 microM, respectively, against MCF7 cells after 48 h of exposure. The structure-relationship activities of each group of compounds are discussed. Bisnaphthalimido compounds are DNA-binding agents. Addition of the bisnaphthalimides PK3, PK4, PK5, PK6 and PK7, at a concentration of 10 microM, to the calf thymus DNA duplex increased the T (m) of DNA by 11.55+/-0.56, 14.545+/-1.59, 6.23+/-2.45, 12.56+/-1.84 and 16.45+/-0.39 degrees C respectively. With the exception of PK5, all compounds bind to DNA by intercalation as judged by effect of compounds on DNA mobility. Ethidium bromide displacement assay showed that all the compounds have significant affinity for calf thymus DNA (the drug concentration required to reduce the fluorescence of initially DNA-bound ethidium bromide by 50%, C(50), was 1.21-17.33 microM). The order of DNA-binding strength was PK4 > PK3 > PK7 > PK6 > PK5. In HL-60 promyelocytic leukaemia cells, oxa-polyamine and bisnaphthalimido treatment resulted in a decline in cell proliferation and viability. The assays performed suggested that apoptosis was not the principal cell death mechanism involved in oxa-polyamine cytotoxicity. In contrast, HL-60 cell death induced by the bisnaphthalimido series was characterized by early exposure of phosphatidylserine exclusive from membrane damage, elevated caspase-3 activity, increased DNA instability and, ultimately, DNA fragmentation. Thus the principal cytotoxic members of the bisnaphthalimido series appear to induce apoptosis.


Subject(s)
Antineoplastic Agents/chemical synthesis , Polyamines/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Humans , Polyamines/chemical synthesis , Structure-Activity Relationship
3.
Life Sci ; 71(10): 1161-73, 2002 Jul 26.
Article in English | MEDLINE | ID: mdl-12095537

ABSTRACT

The growth inhibitory properties of two oxa-spermine derivatives named compound 1 and compound 2, representatives of a novel type of polyamine derivatives, were studied. Dose-response growth inhibitory curves obtained after 48h drug exposure demonstrated the much higher cytotoxic activity of compound 1 towards MCF-7 human breast cancer cells. Further experiments with compound 1 showed that this oxa-spermine derivative exhibited considerable cytotoxicity with IC(50) values of 3.74 microM and 2.93 microM after 24h and 48h drug exposure respectively. In MCF-7 cells, after 8h drug (10 microM) exposure it caused shrinkage, chromatin condensation and nuclear fragmentation. However, no clear DNA laddering was detected in treated cells. Drug treatment provoked an increase in polyamine oxidase (PAO) activity. This enzyme is able to produce cytotoxic H(2)O(2) and 3-acetamidopropanal, catalyzing the oxidative deamination of N(1)-acetylated derivatives of spermine and spermidine to spermidine and putrescine respectively. Taken together these data demonstrate that the novel oxa-polyamine derivative compound 1 has considerable cytotoxic activity towards MCF-7 cells and indicate that an induction of PAO may be involved in its cytotoxic and apoptotic effects.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Spermine/analogs & derivatives , Spermine/pharmacology , Apoptosis/drug effects , Biogenic Polyamines/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/ultrastructure , Cell Division/drug effects , Cell Nucleus/ultrastructure , DNA, Neoplasm/analysis , DNA, Neoplasm/metabolism , Electrophoresis, Agar Gel , Enzyme Induction/drug effects , Female , Humans , Oxidoreductases Acting on CH-NH Group Donors/biosynthesis , Oxidoreductases Acting on CH-NH Group Donors/metabolism , Polyamine Oxidase
4.
Chem Biol Interact ; 137(1): 15-24, 2001 Jul 31.
Article in English | MEDLINE | ID: mdl-11518561

ABSTRACT

Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7 cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These compounds were found to effectively displace the intercalating agent ethidium bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12 microM) and their apparent equilibrium binding constants (K(app)) were calculated to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA without drug). Because of their inherent fluorescence, these compounds were localised preferentially inside the nucleus as evidenced by their direct observation under the fluorescence microscope. The results obtained suggest that the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part, caused by their effects on DNA.


Subject(s)
Cell Division/drug effects , DNA/metabolism , Polyamines/metabolism , Polyamines/pharmacology , Quinolones/metabolism , Quinolones/pharmacology , Spermidine/metabolism , Spermidine/pharmacology , Breast Neoplasms , Female , Humans , Microscopy, Fluorescence , Molecular Structure , Polyamines/chemical synthesis , Polyamines/chemistry , Quinolones/chemical synthesis , Quinolones/chemistry , Spectrometry, Fluorescence , Spermidine/analogs & derivatives , Spermidine/chemical synthesis , Spermidine/chemistry , Tumor Cells, Cultured
5.
J Mol Biol ; 282(5): 1005-11, 1998 Oct 09.
Article in English | MEDLINE | ID: mdl-9753550

ABSTRACT

The DNA hexamer d(CACGPG), in which dP is the ambivalent pyrimidine nucleoside analogue 2'-deoxy-beta-d-ribofuranosyl-(6H,8H-3, 4-dihydropyrimido[4,5-c][1,2]oxazin-7-one), crystallises as a left-handed Z-DNA duplex. X-ray analysis at 1.5 A shows that both P. A base-pairs are of the wobble type. This result appears inconsistent with other evidence from hybridisation and NMR studies of P-containing oligonucleotides, which suggests that, while P can form stable base-pairs with either A or G, thymine-like properties are more pronounced. Thermal denaturation experiments over a range of solution pH values indicate that protonation of the P.A base-pairs is unlikely to be responsible for the anomalous behaviour. No specific crystal packing effects can be identfied as an explanation, and it is concluded that base stacking and other interactions between nucleotide residues in Z-DNA are responsible.


Subject(s)
DNA/chemistry , Deoxyribonucleosides/chemistry , Nucleic Acid Heteroduplexes/chemistry , Thymine/analogs & derivatives , Adenine/chemistry , Crystallography, X-Ray , Hydrogen-Ion Concentration , Models, Molecular , Nucleic Acid Conformation , Oxazines/chemistry , Pyrimidines/chemistry , Thymine/chemistry
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