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The Chinese Journal of Dental Research Sep 2023To test the null hypothesis that dentine treatment with silver diamine fluoride (SDF), a potent antimicrobial agent, following use of proteolytic and chelating agents...
OBJECTIVE
To test the null hypothesis that dentine treatment with silver diamine fluoride (SDF), a potent antimicrobial agent, following use of proteolytic and chelating agents does not influence the wettability of an epoxy resin (AH Plus, Dentsply Sirona, Charlotte, NC, USA) and a tricalcium silicate sealer (BioRoot RCS, Septodont, Saint-Maur-des-Fossés, France).
METHODS
Seventy-two intraradicular dentine specimens were divided into six groups based on the final irrigation solutions used: 2.5% sodium hypochlorite (NaOCl) and 17% ethylenediaminetetraacetic acid (EDTA) (NaOCl-EDTA) (group 1); NaOCl-EDTA-NaOCl (group 2); NaOCl-EDTA followed by 3.8% SDF, NaOCl-EDTA-SDF (group 3); NaOCl-EDTA-NaOCl-SDF (group 4); SDF (group 5) and saline (group 6). After irrigation, the specimens were divided into subgroups according to the sealer used, AH Plus or BioRoot RCS. Contact angles were measured using a contact angle analyser. The data were analysed using an independent t test, one-way analysis of variance (ANOVA) and Tamhane T2 post hoc test, with the level of significance set at P < 0.05.
RESULTS
In the epoxy resin sealer group, dentine surfaces treated with only SDF showed the lowest contact angle. This was significantly less than the groups in which NaOCl was used as the final irrigant (P < 0.05). In the tricalcium silicate-based sealer group, the groups treated with SDF showed significantly greater contact angles when compared to the control group (P < 0.05).
CONCLUSION
It was concluded that SDF conditioning of dentine favours the wettability of epoxy resin sealer but is detrimental to the wettability of tricalcium silicate sealer.
Topics: Wettability; Dental Pulp Cavity; Edetic Acid; Epoxy Resins; Dentin
PubMed: 37732684
DOI: 10.3290/j.cjdr.b4330827 -
British Journal of Pharmacology Sep 2012Amyloid-β (Aβ) aggregation into synaptotoxic, prefibrillar oligomers is a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The...
BACKGROUND AND PURPOSE
Amyloid-β (Aβ) aggregation into synaptotoxic, prefibrillar oligomers is a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The pharmacological and neuroprotective properties of a novel Aβ aggregation inhibitor, SEN1269, were investigated on aggregation and cell viability and in test systems relevant to synaptic function and memory, using both synthetic Aβ(1-42) and cell-derived Aβ oligomers.
EXPERIMENTAL APPROACH
Surface plasmon resonance studies measured binding of SEN1269 to Aβ(1-42) . Thioflavin-T fluorescence and MTT assays were used to measure its ability to block Aβ(1-42) -induced aggregation and reduction in cell viability. In vitro and in vivo long-term potentiation (LTP) experiments measured the effect of SEN1269 on deficits induced by synthetic Aβ(1-42) and cell-derived Aβ oligomers. Following i.c.v. administration of the latter, a complex (alternating-lever cyclic ratio) schedule of operant responding measured effects on memory in freely moving rats.
KEY RESULTS
SEN1269 demonstrated direct binding to monomeric Aβ(1-42) , produced a concentration-related blockade of Aβ(1-42) aggregation and protected neuronal cell lines exposed to Aβ(1-42) . In vitro, SEN1269 alleviated deficits in hippocampal LTP induced by Aβ(1-42) and cell-derived Aβ oligomers. In vivo, SEN1269 reduced the deficits in LTP and memory induced by i.c.v. administration of cell-derived Aβ oligomers.
CONCLUSIONS AND IMPLICATIONS
SEN1269 protected cells exposed to Aβ(1-42) , displayed central activity with respect to reducing Aβ-induced neurotoxicity and was neuroprotective in electrophysiological and behavioural models of memory relevant to Aβ-induced neurodegeneration. It represents a promising lead for designing inhibitors of Aβ-mediated synaptic toxicity as potential neuroprotective agents for treating AD.
Topics: Aminophenols; Amyloid beta-Peptides; Animals; Cell Line; Diamines; Immobilized Proteins; Male; Memory; Molecular Structure; Protein Binding; Pyridazines; Pyrimidines; Rats; Rats, Sprague-Dawley; Synapses
PubMed: 22913627
DOI: 10.1111/j.1476-5381.2012.01973.x -
Accounts of Chemical Research Dec 2014CONSPECTUS: Vicinal diamines are important structural motifs present in various biologically and chemically significant molecules. Direct diamination of olefins provides...
CONSPECTUS: Vicinal diamines are important structural motifs present in various biologically and chemically significant molecules. Direct diamination of olefins provides an effective approach to this class of compounds. Unlike well-established oxidation processes such as epoxidation, dihydroxylation, and aminohydroxylation, direct diamination of olefins had remained a long-standing challenge and had been less well developed. In this Account, we summarize our recent studies on Pd(0)- and Cu(I)-catalyzed diaminations of olefins using di-tert-butyldiaziridinone and its related analogues as nitrogen sources via N-N bond activation. A wide variety of imidazolidinones, cyclic sulfamides, indolines, imidazolinones, and cyclic guanidines can be obtained from conjugated dienes and terminal olefins. For conjugated dienes, the diamination proceeds regioselectively at the internal double bond with the Pd(0) catalyst. Mechanistic studies show that the diamination likely involves a four-membered Pd(II) species resulting from the insertion of Pd(0) into the N-N bond of di-tert-butyldiaziridinone. Interestingly, the Cu(I)-catalyzed process occurs regioselectively at either the terminal or internal double bond depending on the reaction conditions via two mechanistically distinct pathways. The Cu(I) catalyst cleaves the N-N bond of di-tert-butyldiaziridinone to form a Cu(II) nitrogen radical and a four-membered Cu(III) species, which are likely in rapid equilibrium. The Cu(II) nitrogen radical and the four-membered Cu(III) species lead to the terminal and internal diamination, respectively. Terminal olefins are effectively C-H diaminated at the allylic and homoallylic carbons with Pd(0) as catalyst and di-tert-butyldiaziridinone as nitrogen source, likely involving a diene intermediate generated in situ from the terminal olefin via formation of a π-allyl Pd complex and subsequent β-hydride elimination. When di-tert-butylthiadiaziridine 1,1-dioxide is used as nitrogen source, cyclic sulfamides are installed at the terminal carbons via a dehydrogenative diamination process. When α-methylstyrenes (lacking homoallylic hydrogens) react with Pd(0) and di-tert-butyldiaziridinone, spirocyclic indolines are formed with generation of four C-N bonds and one spiro quaternary carbon via allylic and aromatic C-H amination. With Cu(I) catalysts, various terminal olefins can be effectively diaminated at the double bonds using di-tert-butyldiaziridinone, di-tert-butylthiadiaziridine 1,1-dioxide, and 1,2-di-tert-butyl-3-(cyanimino)-diaziridine as nitrogen sources, giving a variety of imidazolidinones, cyclic sulfamides, and cyclic guanidines in good yields, respectively. In the case of monosubstituted olefins using di-tert-butyldiaziridinone as nitrogen source, the resulting diamination products (imidazolidinones) are readily dehydrogenated under the reaction conditions, leading to the corresponding imidazolinones in good yields. Esters can also be diaminated to form the corresponding hydantoins with di-tert-butyldiaziridinone in the presence of a Cu(I) catalyst. A radical mechanism is likely to be operating in these Cu(I)-catalyzed reaction processes. Asymmetric processes have also been developed for the Pd(0)- and Cu(I)-catalyzed diamination reactions. Biologically active compounds such as (+)-CP-99,994 and Sch 425078 have been synthesized via the diamination processes. The diamination reactions described herein provide efficient methods to access a wide variety of vicinal diamines from readily available olefins and show great potential for synthetic applications.
Topics: Alkenes; Amination; Catalysis; Copper; Diamines; Molecular Structure; Nitrogen
PubMed: 25402963
DOI: 10.1021/ar500344t -
Molecules (Basel, Switzerland) Jun 2015Thirteen aminoalcohols and eight diamines were obtained and tested against Trypanosoma cruzi epimastigotes strains MG, JEM and CL-B5 clone. Some of them were equal or...
Thirteen aminoalcohols and eight diamines were obtained and tested against Trypanosoma cruzi epimastigotes strains MG, JEM and CL-B5 clone. Some of them were equal or more potent (1.0-6.6 times) than the reference compound nifurtimox. From them, three aminoalcohols and two diamines were selected for amastigotes assays. Compound 5 was as potent as the reference drug nifurtimox against amastigotes of the CL-B5 strain (IC50 = 0.6 µM), with a selectivity index of 54.
Topics: Alcohols; Animals; Chagas Disease; Chlorocebus aethiops; Diamines; Humans; Trypanocidal Agents; Trypanosoma cruzi; Vero Cells
PubMed: 26111182
DOI: 10.3390/molecules200611554 -
Diagnostic Microbiology and Infectious... Nov 2011Leishmania amazonensis is the etiologic agent of the cutaneous and diffuse leishmaniasis. This species is often associated with drug resistance, and the conventional...
Leishmania amazonensis is the etiologic agent of the cutaneous and diffuse leishmaniasis. This species is often associated with drug resistance, and the conventional treatments exhibit high toxicity for patients. Therefore, the search for new antileishmanial compounds is urgently needed since there is no vaccine available. In this study, using the in vitro traditional drug screening test, we have analyzed the effects of a series of diaminoalkanes monoprotected with t-butyloxycarbonyl (BOC) against L. amazonensis. Among the 18 tested compounds, 6 exhibited antileishmanial activity (2, 7-9, 17, and 18). Best IC(50) values (10.39 ± 0.27 and 3.8 ± 0.42 μg/mL) were observed for compounds 17 and 18 (H(2)N(CH(2))nNHBoc, n = 10 and 12), respectively. Although those compounds had higher lipophilicity as indicated by their cLog P values, compound 17 was very toxic. Determination of the selective indexes indicated that 50% of the active compounds were very toxic for HepG2 cells. However, compounds 2, 8, and 18 had good lipophilicity and were less toxic among all polyamine derivatives tested. The chemical properties of antileishmanial diamine derivatives, such as lipophilicity and cytotoxicity, are relevant factors for the design of new drugs. A higher lipophilicity is likely to improve the chances of reaching this intracellular parasite.
Topics: Animals; Antiprotozoal Agents; Cell Line, Tumor; Diamines; Hep G2 Cells; Humans; Inhibitory Concentration 50; Leishmania; Lethal Dose 50; Macrophages; Mice; Mice, Inbred BALB C
PubMed: 21907525
DOI: 10.1016/j.diagmicrobio.2011.06.011 -
Analytical Sciences : the International... Dec 20012,4-Toluene diamine (TDA), a class A carcinogen, is a major raw material for the production of toluene diisocyanate (TDI), which is one of the precursors for the... (Review)
Review
2,4-Toluene diamine (TDA), a class A carcinogen, is a major raw material for the production of toluene diisocyanate (TDI), which is one of the precursors for the production of polyurethane foams (PU). This review deals with 2,4-toluene diamine's (TDA) carcinogenicity, analytical techniques, biodegradation and use as a biosensor for biogenic and synthetic amines, emphasizing various carcinogenicity studies by 2,4-TDA on animals and humans. This review reports some publications of the analysis of body fluid samples of workers from a PU producing factory for presence of TDA and TDI, since TDI gets absorbed into the worker's body, getting metabolized into TDA. Biodegradations of 2,4-TDA by various researchers are reported and also our own research experience with biodegradation of 2,4-TDA using Aspergillus nidulans isolated from soil site at a polyurethane foam dumping site have been discussed in this review. Biosensors for various biogenic and synthetic amines are discussed.
Topics: Animals; Biodegradation, Environmental; Biosensing Techniques; Carcinogenicity Tests; Carcinogens; Humans; Phenylenediamines
PubMed: 11783783
DOI: 10.2116/analsci.17.1369 -
Nature Communications Feb 2018Saturated 1,4-diazo heterocycles including piperazines, 1,4-diazepanes, and 1,4-diazocanes, are highly important for therapeutic development, but their syntheses are...
Saturated 1,4-diazo heterocycles including piperazines, 1,4-diazepanes, and 1,4-diazocanes, are highly important for therapeutic development, but their syntheses are often tedious. We describe here an amphoteric diamination strategy to unite readily available 1,2-, 1,3- or 1,4-diamine derivatives with electron-deficient allenes via a formal [n + 2] (n = 4, 5, 6) cyclization mode to produce the corresponding 1,4-diazo heterocycles in just one step. This strategy features mild reaction conditions, high functional group tolerance, and scalability (gram scale). The reagents used are cheap and readily available and no transition metal catalysts are needed. More sophisticated products containing trifluoromethyl group or bicyclic ring systems can be accessed via a one-pot procedure as well. Our mechanistic studies support that formation of mono-iodinated or chlorinated diamine intermediates is important for the desired transformation and the commonly proposed chloride-iodide exchange process and a radical N-C bond formation is unlikely when the combination of NCS/KI is used.
Topics: Alkadienes; Cyclization; Diamines; Heterocyclic Compounds; Molecular Structure
PubMed: 29459667
DOI: 10.1038/s41467-018-03085-3 -
Journal of Computer-aided Molecular... Jun 2023N-geranyl-N΄-(2-adamantyl)ethane-1,2-diamine (SQ109) is a tuberculosis drug that has high potency against Mycobacterium tuberculosis (Mtb) and may function by blocking...
N-geranyl-N΄-(2-adamantyl)ethane-1,2-diamine (SQ109) is a tuberculosis drug that has high potency against Mycobacterium tuberculosis (Mtb) and may function by blocking cell wall biosynthesis. After the crystal structure of MmpL3 from Mycobacterium smegmatis in complex with SQ109 became available, it was suggested that SQ109 inhibits Mmpl3 mycolic acid transporter. Here, we showed using molecular dynamics (MD) simulations that the binding profile of nine SQ109 analogs with inhibitory potency against Mtb and alkyl or aryl adducts at C-2 or C-1 adamantyl carbon to MmpL3 was consistent with the X-ray structure of MmpL3 - SQ109 complex. We showed that rotation of SQ109 around carbon-carbon bond in the monoprotonated ethylenediamine unit favors two gauche conformations as minima in water and lipophilic solvent using DFT calculations as well as inside the transporter's binding area using MD simulations. The binding assays in micelles suggested that the binding affinity of the SQ109 analogs was increased for the larger, more hydrophobic adducts, which was consistent with our results from MD simulations of the SQ109 analogues suggesting that sizeable C-2 adamantyl adducts of SQ109 can fill a lipophilic region between Y257, Y646, F260 and F649 in MmpL3. This was confirmed quantitatively by our calculations of the relative binding free energies using the thermodynamic integration coupled with MD simulations method with a mean assigned error of 0.74 kcal mol compared to the experimental values.
Topics: Antitubercular Agents; Molecular Dynamics Simulation; Bacterial Proteins; Membrane Transport Proteins; Mycobacterium tuberculosis; Ethylenediamines
PubMed: 37129848
DOI: 10.1007/s10822-023-00504-6 -
Analytical Sciences : the International... Feb 2021A convenient and uncomplicated scheme has been projected for the quantitative determination of essential diamines putrescine (PUT) and cadaverine (CAD) via sodium...
A convenient and uncomplicated scheme has been projected for the quantitative determination of essential diamines putrescine (PUT) and cadaverine (CAD) via sodium dodecyl sulfate protected silver nanoparticles (SDS-AgNPs). This scheme is based on the chemical interaction of a SDS-AgNPs probe with PUT and CAD, leading to a color change from yellow to red or reddish brown. The interaction was investigated through different techniques such as using a UV-visible spectrophotometer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), dynamic light scattering spectroscopy (DLS) and the zeta potential. Both amines possess a close resemblance in structure (except for the addition of one more methylene group in CAD), and no any distinguishable color change was noted. However, the maximum absorption band at 580 and 600 nm was demonstrated for PUT and CAD correspondingly. The methodical response was observed at absorption ratios of 580/410 and 600/410 nm, with the linear regression within 4 - 12 and 6 - 14 μg/mL for PUT and CAD. The detection limits calculated for both the diamines PUT and CAD were 0.333 and 1.638 μg/mL. The scheme was successfully applied for determinations in biological samples, including spiked blood plasma and urine. Putrescine exhibited % recovery within 95.717 - 105.200%, while cadaverine was within 95.940 - 105.109%, respectively. The scheme was reproducible and precise with inter-day RSD (n = 5) within 1.126, 0.018% and the intraday RSD (n = 5) was within 0.005, 0.002% for PUT and CAD, respectively.
Topics: Cadaverine; Colorimetry; Healthy Volunteers; Humans; Metal Nanoparticles; Putrescine; Silver; Sodium Dodecyl Sulfate
PubMed: 32779576
DOI: 10.2116/analsci.20P153 -
Bioorganic Chemistry May 2021MutT Homolog 1 (MTH1) has been proven to hydrolyze oxidized nucleotide triphosphates during DNA repair. It can prevent the incorporation of wrong nucleotides during DNA...
MutT Homolog 1 (MTH1) has been proven to hydrolyze oxidized nucleotide triphosphates during DNA repair. It can prevent the incorporation of wrong nucleotides during DNA replication and mitigate cell apoptosis. In a cancer cell, abundant reactive oxygen species can lead to substantial DNA damage and DNA mutations by base-pairing mismatch. MTH1 could eliminate oxidized dNTP and prevent cancer cells from entering cell death. Therefore, inhibition of MTH1 activity is considered to be an anti-cancer therapeutic target. In this study, high-throughput screening techniques were combined with a fragment-based library containing 2,313 compounds, which were used to screen for lead compounds with MTH1 inhibitor activity. Four compounds with MTH1 inhibitor ability were selected, and compound MI0639 was found to have the highest effective inhibition. To discover the selectivity and specificity of this action, several derivatives based on the MTH1 and MI0639 complex structure were synthesized. We compared 14 complex structures of MTH1 and the various compounds in combination with enzymatic inhibition and thermodynamic analysis. Nanomolar-range IC inhibition abilities by enzyme kinetics and K values by thermodynamic analysis were obtained for two compounds, named MI1020 and MI1024. Based on structural information and compound optimization, we aim to provide a strategy for the development of MTH1 inhibitors with high selectivity and specificity.
Topics: Antineoplastic Agents; Binding Sites; Cell Line, Tumor; Cell Proliferation; DNA Repair Enzymes; Diamines; Dose-Response Relationship, Drug; Drug Development; Drug Screening Assays, Antitumor; Enzyme Inhibitors; High-Throughput Screening Assays; Humans; Molecular Structure; Phosphoric Monoester Hydrolases; Structure-Activity Relationship; Substrate Specificity; Thermodynamics
PubMed: 33774493
DOI: 10.1016/j.bioorg.2021.104813