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The Biochemical Journal Oct 19771. The activity of ornithine decarboxylase in the liver and kidneys of rats maintained on a cyclical regimen of protein-free and protein-containing diets was...
Ornithine decarboxylase and polyamines in liver and kidneys of rats on cyclical regimen of protein-free and protein-containing diets. Relationship to deoxyribonucleic acid synthesis in liver.
1. The activity of ornithine decarboxylase in the liver and kidneys of rats maintained on a cyclical regimen of protein-free and protein-containing diets was investigated. There was a daily activation of the enzyme in response to the feeding of protein after 3 days feeding of protein-free diet. 2. The activation of ornithine decarboxylase in the liver and kidneys of rats re-fed on protein was demonstrable throughout 16 cycles of alternating 3-day periods of protein-free and protein-containing diets. The magnitude of the activation in the kidneys diminished from 20-fold stimulation in the first cycle to 5-fold stimulation (compared with animals fed with protein-free diet) in the later cycles of protein re-feeding. The activation of the enzyme in liver was decreased from 20-fold stimulation in the first cycle to approx. 10-fold stimulation in later cycles. 3. The concentration of spermidine was increased by approx. 50% in the liver of animals during cycling from protein-free to protein-containing diets. Spermine was unchanged, and putrescine was maintained at a low concentration approx. one-fifth to one-tenth that of spermidine after protein re-feeding. 4. The incorporation of [(3)H]thymidine into liver DNA was increased 10-fold in animals re-fed with protein compared with animals receiving protein-free diets. 5. The activation of ornithine decarboxylase by re-feeding of protein was inhibited 90% by the injection of propane-1,3-diamine during re-feeding. The stimulation of DNA synthesis was inhibited 60% by multiple injections of propane-1,3-diamine during the re-feeding of protein.
Topics: Animals; Carboxy-Lyases; DNA; Diamines; Dietary Proteins; Kidney; Liver; Male; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Periodicity; Polyamines; Protein Deficiency; Rats
PubMed: 597262
DOI: 10.1042/bj1680049 -
British Journal of Pharmacology Jan 2005SQ109 is a novel [1,2]-diamine-based ethambutol (EMB) analog developed from high-throughput combinatorial screening. The present study aimed at characterizing its... (Comparative Study)
Comparative Study
SQ109 is a novel [1,2]-diamine-based ethambutol (EMB) analog developed from high-throughput combinatorial screening. The present study aimed at characterizing its pharmacodynamics and pharmacokinetics. The antimicrobial activity of SQ109 was confirmed in vitro (Mycobacterium tuberculosis-infected murine macrophages) and in vivo (M. tuberculosis-infected C57BL/6 mice) and compared to isoniazid (INH) and EMB. SQ109 showed potency and efficacy in inhibiting intracellular M. tuberculosis that was similar to INH, but superior to EMB. In vivo oral administration of SQ109 (0.1-25 mg kg(-1) day(-1)) to the mice for 28 days resulted in dose-dependent reductions of mycobacterial load in both spleen and lung comparable to that of EMB administered at 100 mg kg(-1) day(-1), but was less potent than INH at 25 mg kg(-1) day(-1). Monitoring of SQ109 levels in mouse tissues on days 1, 14 and 28 following 28-day oral administration (10 mg kg(-1) day(-1)) revealed that lungs and spleen contained the highest concentration of SQ109, at least 10 times above its MIC. Pharmacokinetic profiles of SQ109 in mice following a single administration showed its C(max) as 1038 (intravenous (i.v.)) and 135 ng ml(-1) (p.o.), with an oral T(max) of 0.31 h. The elimination t(1/2) of SQ109 was 3.5 (i.v.) and 5.2 h (p.o.). The oral bioavailability was 4%. However, SQ109 displayed a large volume of distribution into various tissues. The highest concentration of SQ109 was present in lung (>MIC), which was at least 120-fold (p.o.) and 180-fold (i.v.) higher than that in plasma. The next ranked tissues were spleen and kidney. SQ109 levels in most tissues after a single administration were significantly higher than that in blood. High tissue concentrations of SQ109 persisted for the observation period (10 h). This study demonstrated that SQ109 displays promising in vitro and in vivo antitubercular activity with favorable targeted tissue distribution properties.
Topics: Administration, Oral; Animals; Antitubercular Agents; Biological Availability; Cell Line; Diamines; Dose-Response Relationship, Drug; Drug Administration Schedule; Ethambutol; Female; Injections, Intravenous; Isoniazid; Macrophages; Mice; Mice, Inbred C57BL; Molecular Structure; Mycobacterium tuberculosis; Tissue Distribution; Tuberculosis
PubMed: 15644871
DOI: 10.1038/sj.bjp.0705984 -
Chemical Research in Toxicology Nov 2021Interstrand DNA cross-links are important in biology, medicinal chemistry, and materials science. Accordingly, methods for the targeted installation of interstrand...
Synthesis of DNA Duplexes Containing Site-Specific Interstrand Cross-Links via Sequential Reductive Amination Reactions Involving Diamine Linkers and Abasic Sites on Complementary Oligodeoxynucleotides.
Interstrand DNA cross-links are important in biology, medicinal chemistry, and materials science. Accordingly, methods for the targeted installation of interstrand cross-links in DNA duplexes may be useful in diverse fields. Here, a simple procedure is reported for the preparation of DNA duplexes containing site-specific, chemically defined interstrand cross-links. The approach involves sequential reductive amination reactions between diamine linkers and two abasic (apurinic/apyrimidinic, AP) sites on complementary oligodeoxynucleotides. Use of the symmetrical triamine, tris(2-aminoethyl)amine, in this reaction sequence enabled the preparation of a cross-linked DNA duplex bearing a derivatizable aminoethyl group.
Topics: Amination; Cross-Linking Reagents; DNA; Diamines; Molecular Structure; Oligodeoxyribonucleotides
PubMed: 34694787
DOI: 10.1021/acs.chemrestox.1c00293 -
Scientific Reports Nov 2022The uncontrolled oxidative decomposition of electrolyte while operating at high potential (> 4.2 V vs Li/Li) severely affects the performance of high-energy density...
The uncontrolled oxidative decomposition of electrolyte while operating at high potential (> 4.2 V vs Li/Li) severely affects the performance of high-energy density transition metal oxide-based materials as cathodes in Li-ion batteries. To restrict this degradative response of electrolyte species, the need for functional molecules as electrolyte additives that can restrict the electrolytic decomposition is imminent. In this regard, bio-derived molecules are cost-effective, environment friendly, and non-toxic alternatives to their synthetic counter parts. Here, we report the application of microbially synthesized 2,5-dimethyl-3,6-bis(4-aminobenzyl)pyrazine (DMBAP) as an electrolyte additive that stabilizes high-voltage (4.5 V vs Li/Li) LiNiMnCoO cathodes. The high-lying highest occupied molecular orbital of bio-additive (DMBAP) inspires its sacrificial in situ oxidative decomposition to form an organic passivation layer on the cathode surface. This restricts the excessive electrolyte decomposition to form a tailored cathode electrolyte interface to administer cyclic stability and enhance the capacity retention of the cathode.
Topics: Diamines; Pyrazines; Electrodes; Lithium; Ions; Oxides
PubMed: 36434117
DOI: 10.1038/s41598-022-22018-1 -
Molecules (Basel, Switzerland) Oct 2022The efficient "One-pot" CuCl-catalyzed C-S bond coupling reactions were developed for the synthesis of dibenzo[,][1,4]thiazepines and...
The efficient "One-pot" CuCl-catalyzed C-S bond coupling reactions were developed for the synthesis of dibenzo[,][1,4]thiazepines and 11-methy-ldibenzo[,][1,4]thiazepines via 2-iodobenzaldehydes/2-iodoacetophenones with 2-aminobenzenethiols/2,2'-disulfanediyldianilines by using bifunctional-reagent N, N'-dimethylethane-1,2-diamine (DMEDA), which worked as ligand and reductant. The reactions were compatible with a range of substrates to give the corresponding products in moderate to excellent yields.
Topics: Diamines; Catalysis; Indicators and Reagents; Dibenzothiazepines; Thiazepines
PubMed: 36364217
DOI: 10.3390/molecules27217392 -
Biomedicine & Pharmacotherapy =... Jul 2021Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the...
Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria.
Topics: 3T3 Cells; Animals; Apoptosis; Cell Death; Cell Line; Chlorocebus aethiops; Diamines; Female; Humans; Metronidazole; Mice; Parasites; Peptide Hydrolases; Quinazolines; Trichomonas Vaginitis; Trichomonas vaginalis; Vero Cells
PubMed: 34243597
DOI: 10.1016/j.biopha.2021.111611 -
Yakugaku Zasshi : Journal of the... Aug 2010This review describes the first method to prepare imidazolines from aldehydes and 1,2-diamines by condensation and successive oxidation using NBS in one-pot operation.... (Review)
Review
This review describes the first method to prepare imidazolines from aldehydes and 1,2-diamines by condensation and successive oxidation using NBS in one-pot operation. The reaction proceeds under mild conditions and can be applied to various aromatic and aliphatic aldehydes and 1,2-diamines. The utility of this method is also demonstrated in the total synthesis of spongotine A and the preparation of a newly designed organocatalyst, C3-symmetric trisimidazoline 7.
Topics: Aldehydes; Catalysis; Diamines; Imidazolines; Indole Alkaloids; Indoles; Organic Chemistry Phenomena; Oxidation-Reduction
PubMed: 20686205
DOI: 10.1248/yakushi.130.1011 -
Molecules (Basel, Switzerland) Nov 2019A novel and convenient approach for the solid-phase 5'-functionalization of oligonucleotides is proposed in this article. The approach is based on the activation of free...
A novel and convenient approach for the solid-phase 5'-functionalization of oligonucleotides is proposed in this article. The approach is based on the activation of free 5'-hydroxyl of polymer support-bound protected oligonucleotides by ,'-disuccinimidyl carbonate followed by interaction with amino-containing ligands. Novel amino-containing derivatives of -dodecaborate, estrone, cholesterol, and α-tocopherol were specially prepared. A wide range of oligonucleotide conjugates bearing -dodecaborate, short peptide, pyrene, lipophilic residues (cholesterol, α-tocopherol, folate, estrone), aliphatic diamines, and propargylamine were synthesized and characterized to demonstrate the versatility of the approach. The developed method is suitable for the conjugate synthesis of oligonucleotides of different types (ribo-, deoxyribo-, 2'--methylribo-, and others).
Topics: Boron Compounds; Diamines; Molecular Structure; Oligonucleotides; Pargyline; Propylamines; Pyrenes; Solid-Phase Synthesis Techniques
PubMed: 31771111
DOI: 10.3390/molecules24234266 -
Molecules (Basel, Switzerland) Mar 2020A three-component reaction between diamines (diaminobenzenes, diaminocyclohexanes, and piperazines), triethyl orthoformate, and diethyl phosphite was studied in some...
A three-component reaction between diamines (diaminobenzenes, diaminocyclohexanes, and piperazines), triethyl orthoformate, and diethyl phosphite was studied in some detail. In the case of 1,3- and 1,4-diamines and piperazines, products of the substitution of two amino moieties-the corresponding tetraphosphonic acids-were obtained. In the cases of 1,2-diaminobenzene, 1,2-diaminocyclohexanes and 1,2-diaminocyclohexenes, only one amino group reacted. This is most likely the result of the formation of hydrogen bonding between the phosphonate oxygen and a hydrogen of the adjacent amino group, which caused a decrease in the reactivity of the amino group. Most of the obtained compounds inhibited the proliferation of RAW 264.7 macrophages, PC-3 human prostate cancer cells, and MCF-7 human breast cancer cells, with 1, trans-7, and 16 showing broad nonspecific activity, which makes these compounds especially interesting in the context of anti-osteolytic treatment and the blocking of interactions and mutual activation of osteoclasts and tumor metastatic cells. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid, which were used as controls. However, studies of sheep with induced osteoporosis carried out with compound trans-7 did not support this assumption.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Chemistry Techniques, Synthetic; Diamines; Humans; MCF-7 Cells; Magnetic Resonance Spectroscopy; Mice; Osteoclasts; Phosphites; Structure-Activity Relationship
PubMed: 32245019
DOI: 10.3390/molecules25061424 -
Medical Science Monitor : International... Jul 2019BACKGROUND T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy caused by abnormal proliferation of immature T cell progenitors....
BACKGROUND T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy caused by abnormal proliferation of immature T cell progenitors. Chemotherapy of T-ALL usually consists of induction, consolidation, and long-term maintenance. Diacetyl hexamethylene diamine (CAHB) is a newly developed agent that induces the differentiation of malignant cells and deprives their clonal growth ability. Since its effect on T-ALL has not been previously determined, we evaluated its potential function in the Jurkat cell line. MATERIAL AND METHODS MTT assay was conducted to evaluate the cytotoxicity and anti-proliferative effect of CAHB. The apoptosis level of CAHB-treated Jurkat cells was evaluated using flow cytometry via staining with Annexin V/PI or cleaved-caspase-3. The alteration of mitochondrial membrane potential was determined by flow cytometry. The expression of Bax and Bcl-2 was evaluated by RT-PCR and Western blot. Western blot was also used to assess the activation of Akt. RESULTS CAHB inhibited the proliferation and promoted the apoptosis of Jurkat cells in a time- and dose-dependent manner by decreasing activation of Akt, reducing the mitochondrial membrane potential, and downregulating the Bcl-2/Bax ratio. CONCLUSIONS Our data suggest that CAHB might be regarded as a novel treatment agent for T-ALL since it can induce apoptosis and inhibit proliferation of the T-ALL cell line at a relatively low level.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Proliferation; Cell Survival; Diacetyl; Diamines; Down-Regulation; Humans; Jurkat Cells; Membrane Potential, Mitochondrial; Phosphatidylinositol 3-Kinases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Signal Transduction
PubMed: 31301225
DOI: 10.12659/MSM.915840