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Chemical & Pharmaceutical Bulletin 2021In this study, a series of alkyl diamine linked bivalent β-carbolines was synthesized and evaluated as antitumor agent. The results demonstrated that most compounds...
In this study, a series of alkyl diamine linked bivalent β-carbolines was synthesized and evaluated as antitumor agent. The results demonstrated that most compounds displayed good antiproliferative activities with IC value lower than 10 µM against a panel of human tumor cell lines, and compound 8 was found to be the most potent antiproliferative agent with IC value of 1.39, 1.96, 1.42, 1.49, 1.32, 1.96 and 1.63 µM against human breast cancer cell line (MCF-7), human adenocarcinoma cell line (769-P), human malighant melanoma cell line (A375), human ovarian cancer cell line (SK-OV-3), human colon carcinoma cell line (HCT-116), human gastric cancer cell line (BGC-823) and human esophageal squamous carcinoma cell line (Eca-109), respectively. Further investigations on mechanism of action of this class of compound demonstrated that the representative compound 8 inhibited colorectal cancer growth through inducing autophagy.
Topics: Antineoplastic Agents; Apoptosis; Autophagy; Carbolines; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Diamines; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Reactive Oxygen Species; Structure-Activity Relationship
PubMed: 34719593
DOI: 10.1248/cpb.c21-00588 -
The Journal of Organic Chemistry Nov 2022A highly efficient enantioselective α-nitrogenation method of α,α-disubstituted aldehydes with azodicarboxylates promoted by a chiral carbamate-monoprotected...
A highly efficient enantioselective α-nitrogenation method of α,α-disubstituted aldehydes with azodicarboxylates promoted by a chiral carbamate-monoprotected cyclohexa-1,2-diamine as organocatalyst has been developed. The process was carried out without any solvent, and the corresponding α,α-disubstituted α-nitrogenated aldehydes were obtained with excellent yields and enantioselectivities up to 99% . The sustainability of the procedure was established through the calculation of green metrics, such as EcoScale and E-factor. In addition, theoretical calculations have been used to justify the obtained enantioselectivity sense.
Topics: Aldehydes; Stereoisomerism; Solvents; Catalysis; Diamines
PubMed: 36283071
DOI: 10.1021/acs.joc.2c01919 -
Biomolecules Jul 2021Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant....
Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant. Here, we asked whether PrC-210 would suppress damage seen in allograft kidney transplant. Brown Norway (BN) rat kidneys were perfused in situ (UW Solution) with or without added 30 mM PrC-210, and then immediately transplanted into Lewis (LEW) rats. 20 h later, the transplanted BN kidneys and LEW rat plasma were analyzed. Kidney histology, and kidney/serum levels of several inflammation-associated cytokines, were measured to assess mismatch-related kidney pathology, and PrC-210 protective efficacy. Twenty hours after the allograft transplants: (i) significant histologic kidney tubule damage and mononuclear inflammatory cell infiltration were seen in allograft kidneys; (ii) kidney function metrics (creatinine and BUN) were significantly elevated; (iii) significant changes in key cytokines, i.e., TIMP-1, TNF-alpha and MIP-3A/CCL20, and kidney activated caspase levels were seen. In PrC-210-treated kidneys and recipient rats, (i) kidney histologic damage (Banff Scores) and mononuclear infiltration were reduced to untreated background levels; (ii) creatinine and BUN were significantly reduced; and (iii) activated caspase and cytokine changes were significantly reduced, some to background. In conclusion, the results suggest that PrC-210 could provide broadly applicable organ protection for many allograft transplantation conditions; it could protect transplanted kidneys during and after all stages of the transplantation process-from organ donation, through transportation, re-implantation and the post-operative inflammation-to minimize acute and chronic rejection.
Topics: Adenosine; Allografts; Allopurinol; Animals; Caspases; Creatinine; Cytokines; Diamines; Free Radical Scavengers; Glutathione; Inflammation; Insulin; Kidney; Kidney Transplantation; Male; Mitochondria; Organ Preservation Solutions; Raffinose; Rats, Inbred BN; Rats, Inbred Lew; Sulfhydryl Compounds; Rats
PubMed: 34356678
DOI: 10.3390/biom11071054 -
PLoS Computational Biology Jan 2018Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior. Two of the best-characterized death smell components are putrescine...
Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior. Two of the best-characterized death smell components are putrescine (PUT) and cadaverine (CAD), foul-smelling molecules produced by decarboxylation of amino acids during decomposition. These volatile polyamines act as 'necromones', triggering avoidance or attractive responses, which are fundamental for the survival of a wide range of species. The few studies that have attempted to identify the cognate receptors for these molecules have suggested the involvement of the seven-helix trace amine-associated receptors (TAARs), localized in the olfactory epithelium. However, very little is known about the precise chemosensory receptors that sense these compounds in the majority of organisms and the molecular basis of their interactions. In this work, we have used computational strategies to characterize the binding between PUT and CAD with the TAAR6 and TAAR8 human receptors. Sequence analysis, homology modeling, docking and molecular dynamics studies suggest a tandem of negatively charged aspartates in the binding pocket of these receptors which are likely to be involved in the recognition of these small biogenic diamines.
Topics: Animals; Aspartic Acid; Behavior, Animal; Cadaverine; Cell Cycle Proteins; Computational Biology; Computer Simulation; Diamines; Humans; Ligands; Molecular Docking Simulation; Nuclear Proteins; Olfactory Mucosa; Phylogeny; Polyamines; Protein Binding; Putrescine; Receptors, G-Protein-Coupled; Smell; Zebrafish
PubMed: 29324768
DOI: 10.1371/journal.pcbi.1005945 -
Polish Journal of Microbiology 2009Introduction of a new antimicrobial agent as a drug--for treatment of infections or as a disinfectant and antiseptic, may result in the occurrence of resistance...
Introduction of a new antimicrobial agent as a drug--for treatment of infections or as a disinfectant and antiseptic, may result in the occurrence of resistance mechanisms against this agent among microorganisms. Two disinfectants of different composition--Incidin Plus for surface disinfection and Sekusept Plus for medical devices disinfection, both containing glucoprotamin as the active substance, were investigated in this study in order to analyze their antimicrobial activity. Standard bacterial and fungal strains recommended by European Standards, established by European Standardization Committee for testing bactericidal and fungicidal activity of chemical disinfectants were used in the study. Furthermore, 60 clinical bacterial strains with different susceptibility to antibiotics and chemotherapeutics, mostly multiresistant, isolated from different specimens from hospitalized patients were analyzed. In addition, 184 fungal clinical strains isolated from hospitalized patients and outpatients were also included in this study. Antimicrobial activity was evaluated according to EN 1040:2005 --using bacterial strains and according to EN 1275:2005--using fungal strains. Glucoprotamin proved to be a very effective and rapidly acting bactericidal and fungicidal agent. Low concentration of glucoprotamin--0.5% showed to be very effective (1 min) against clinical bacterial isolates. Incidin Plus was also very effective (5 min) against clinical fungal isolates.
Topics: Bacteria; Diamines; Disinfectants; Fungi; Pyrrolidinones
PubMed: 20380145
DOI: No ID Found -
ACS Nano Oct 2022Semiconductor-based photoredox catalysis brings an innovative strategy for sustainable organic transformation (e.g., C-C/C-X bond formation), via radical coupling under...
Semiconductor-based photoredox catalysis brings an innovative strategy for sustainable organic transformation (e.g., C-C/C-X bond formation), via radical coupling under mild conditions. However, since semiconductors interact with photogenerated radicals unselectively, the precise control of selectivity for such organic synthesis by steering radical conversion is extremely challenging. Here, by the judicious design of a structurally well-defined and atomically dispersed cocatalyst over semiconductor quantum dots, we demonstrate the precise selectivity switch on high-performance selective heterogeneous coupling photosynthesis of a C-C bond or a C-N bond along with hydrogen production over the Ni-oxo cluster and single Pd atom-decorated CdS quantum dots crafted onto the SiO support. Mechanistic studies unveil that the Ph(CH)NH and PhCHNH act as dominant radical intermediates for such divergent organic synthesis of C-C coupled vicinal diamines and C-N coupled imines, as respectively enabled by Ni-oxo clusters assisted radical-radical coupling and single Pd atom-assisted radical addition-elimination. This work overcomes the pervasive difficulties of selectivity regulation in semiconductor-based photochemical synthesis, highlighting a vista of utilizing atomically dispersed cocatalysts as active sites to maneuver unselective radical conversion by engineering quantum dots toward selective heterogeneous photosynthesis.
Topics: Quantum Dots; Silicon Dioxide; Semiconductors; Photosynthesis; Hydrogen; Diamines; Imines
PubMed: 36170635
DOI: 10.1021/acsnano.2c08652 -
International Journal of Pharmaceutics Jul 2018The poly(cystaminebis(acrylamide)-diaminohexane) (poly(CBA-DAH)) was designed previously as a bio-reducible efficient gene delivery carrier. However, the high weight...
The poly(cystaminebis(acrylamide)-diaminohexane) (poly(CBA-DAH)) was designed previously as a bio-reducible efficient gene delivery carrier. However, the high weight ratio required to form the polyplexes between poly(CBA-DAH) with pDNA is still a problem that needs to be addressed. To solve this problem and increase the transfection efficiency, poly(ethylenimine) (PEI, 1.8 kDa) was conjugated to poly(CBA-DAH) via disulfide bond. The PEI conjugated poly(CBA-DAH) (PCDP) can bind with pDNA at a very low weight ratio of 0.5 and above, like PEI 25 kDa, and form the polyplexes with nano-size (102-128 nm) and positive surface charge (27-34 mV). PCDP and PCDP polyplexes had negligible cytotoxicity and indicated similar or better cellular uptake than the comparison groups such as PEI 25 kDa and Lipofectamine® polyplexes. To confirm the transfection efficiency, the plasmid DNA (pDNA) encoded with the luciferase reporter gene (gWiz-Luc) and green fluorescent protein reporter gene (GFP) were used and treated with PCDP into the A549, Huh-7, and Mia PaCa-2 cells. PCDP/pDNA polyplexes showed highest transfection efficiency in all tested cell lines. In the luciferase assay, PCDP polyplexes showed 10.2 times higher gene transfection efficiency than Lipofectamine® polyplexes in mimic in vivo conditions (30% FBS, A549 cells). The VEGF siRNA expressing plasmid (pshVEGF), which is constructed as a therapeutic gene by our previous work, was delivered by PCDP into the cancer cells. The VEGF gene expression of PCDP/pshVEGF polyplexes was dramatically lower than control and the VEGF gene silencing efficiencies of PCDP/pshVEGF (w/w; 10/1) polyplexes were 54% (A549 cells), 77% (Huh-7 cells), and 66% (Mia PaCa-2 cells). In addition, PCDP/pshVEGF had reduced cell viability rates of about 31% (A549 cells), 39% (Huh-7 cells), and 42% (Mia PaCa-2 cells) and showed better results than all comparison groups. In the transfection efficiency and VEGF silencing assay, PCDP polyplexes showed better results than poly(CBA-DAH) at 4-fold lower weight ratio. The data of all experiments demonstrate that the synthesized PCDP could be used for efficient gene delivery and could be widely applied.
Topics: A549 Cells; Acrylamides; Diamines; Gene Expression Regulation, Neoplastic; Gene Transfer Techniques; Genes, Reporter; Humans; Imines; Nanoparticles; Neoplasms; Particle Size; Plasmids; Polyethylenes; RNA Interference; RNA, Small Interfering; Surface Properties; Transfection; Vascular Endothelial Growth Factor A
PubMed: 29698820
DOI: 10.1016/j.ijpharm.2018.04.051 -
Molecules (Basel, Switzerland) Oct 2022Diisocyanates are highly reactive compounds with two functional isocyanate groups. The exposure of diisocyanates is associated with severely adverse health effects, such...
Diisocyanates are highly reactive compounds with two functional isocyanate groups. The exposure of diisocyanates is associated with severely adverse health effects, such as asthma, inflammation in the respiratory tract, and cancer. The hydrolysis product from diisocyanates to related diamines is also a potential carcinogen. Here, we developed an effective, accurate, and precise method for simultaneous determination of residual diisocyanates and related diamines in biodegradable mulch films, based on N-ethoxycarbonylation derivatization and gas chromatography-mass spectrometry. The method development included the optimization of ultrasonic hydrolysis and extraction, screening of N-ethoxycarbonylation conditions with ethyl chloroformate, evaluation of the diamines degradation, and analysis of the fragmentation mechanisms. Under the optimum experimental conditions, good linearity was observed with R2 > 0.999. The extraction recoveries were found in the range of 93.9−101.2% with repeatabilities and reproducibilities in 0.89−8.12% and 2.12−10.56%, respectively. The limits of detection ranged from 0.0025 to 0.057 µg/mL. The developed method was applied to commercial polybutylene adipate co-terephthalate (PBAT) biodegradable mulch film samples for analysis of the diverse residual diisocyanates and related diamine additives. The components varied greatly among the sample from different origin. Overall, this study provides a reliable method for assessing safety in biodegradable mulch films.
Topics: Carcinogens; Diamines; Gas Chromatography-Mass Spectrometry; Isocyanates
PubMed: 36235287
DOI: 10.3390/molecules27196754 -
Nature Communications Dec 2022Vicinal diamines are privileged synthetic motifs in chemistry due to their prevalence and powerful applications in bioactive molecules, pharmaceuticals, and ligand...
Vicinal diamines are privileged synthetic motifs in chemistry due to their prevalence and powerful applications in bioactive molecules, pharmaceuticals, and ligand design for transition metals. With organic diazides being regarded as modular precursors to vicinal diamines, enormous efforts have been devoted to developing efficient strategies to access organic diazide generated from olefins, themselves common feedstock chemicals. However, state-of-the-art methods for alkene diazidation rely on the usage of corrosive and expensive oxidants or complicated electrochemical setups, significantly limiting the substrate tolerance and practicality of these methods on large scale. Toward overcoming these limitations, here we show a photochemical diazidation of alkenes via iron-mediated ligand-to-metal charge transfer (LMCT) and radical ligand transfer (RLT). Leveraging the merger of these two reaction manifolds, we utilize a stable, earth abundant, and inexpensive iron salt to function as both radical initiator and terminator. Mild conditions, broad alkene scope and amenability to continuous-flow chemistry rendering the transformation photocatalytic were demonstrated. Preliminary mechanistic studies support the radical nature of the cooperative process in the photochemical diazidation, revealing this approach to be a powerful means of olefin difunctionalization.
Topics: Alkenes; Ligands; Catalysis; Iron; Diamines
PubMed: 36564375
DOI: 10.1038/s41467-022-35560-3 -
International Journal of Molecular... Sep 2023Systematic studies of crystalline compounds formed in aqueous systems containing aliphatic diamines, divalent transition metal halides, and selenious acid resulted in...
Protonated Organic Diamines as Templates for Layered and Microporous Structures: Synthesis, Crystal Chemistry, and Structural Trends among the Compounds Formed in Aqueous Systems Transition Metal Halide or Nitrate-Diamine-Selenious Acid.
Systematic studies of crystalline compounds formed in aqueous systems containing aliphatic diamines, divalent transition metal halides, and selenious acid resulted in the discovery of a large family of new complex species corresponding to several new structure types. With ethylenediamine (en), layered (enH)[(HSeO)] compounds are the most commonly formed species which constitute a significant contribution to the family of layered hydrogen selenites containing neutral [(HSeO)] ( = Mg, Mn, Co, Ni, Cu, Zn, Cd) 2 building blocks. In contrast to some previous suggestions, piperazine (pip), as well as its homologue N-methylpiperazine, mostly give rise to quite different, sometimes more complex, structures of varied dimensionality while the (pipH)[(HSeO)] compounds are formed only with = Cu and Cd. In addition, metal-, halide-, or selenium-free by-product species are observed. The Se can be present in a multitude of forms, including HSeO, HSeO, SeO, and SeO, reflecting amazing adaptability to the shape of the templating cations.
Topics: Nitrates; Diamines; Cadmium; Inorganic Chemicals; Selenious Acid; Transition Elements
PubMed: 37762505
DOI: 10.3390/ijms241814202