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Natural Product Reports Mar 2020Covering: 2006 to 2019Macrocyclic diamine alkaloids derived from 3-alkyldihydropyridine dimers comprise a diverse and highly complex family of natural products. The... (Review)
Review
Covering: 2006 to 2019Macrocyclic diamine alkaloids derived from 3-alkyldihydropyridine dimers comprise a diverse and highly complex family of natural products. The macrocyclic and caged structural features of these alkaloids have inspired many creative solutions from the synthetic organic community over the past 30 years. This review will cover the successful synthetic campaigns over the past decade, with a focus on (1) key bond disconnections and advances and (2) remaining challenges and opportunities for innovation within this natural product class.
Topics: Alkaloids; Biological Products; Bridged-Ring Compounds; Carbazoles; Carbolines; Diamines; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Piperidines; Quinolizidines; Quinolizines; Spiro Compounds
PubMed: 31524907
DOI: 10.1039/c9np00031c -
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 -
Environmental Science & Technology Nov 2018The high energy requirement of amine regeneration and the uncertainty of safe disposal of the captured CO remain big challenges to the large-scale implementation of...
The high energy requirement of amine regeneration and the uncertainty of safe disposal of the captured CO remain big challenges to the large-scale implementation of amine scrubbing process for CO capture. Mineral carbonation represents a safe and permanent route to capture and store CO with net energy production but typically proceeds at a slow reaction rate. Here, we present a new integrated absorption and mineralization (IAM) process that couples a diamine-based CO absorption with fly-ash-triggered amine regeneration. The technical feasibility of the IAM process using 3-diethylaminopropylamine (DEAPA) and CaO-containing materials such as CaO and coal fly ashes was verified, and the reaction mechanism involved was investigated. It was found that CaO and CaO-rich coal fly ash were effective to regenerate DEAPA via the decomposition of DEAPA carbamate species and the formation of calcium carbonate precipitates. Furthermore, the diamine-based IAM process displayed a fast kinetics and a high stability for CO sequestration and can reduce the leachability of some heavy metals in the fly ash. These process properties render this diamine-based IAM process a great potential for carbon capture and sequestration applications.
Topics: Carbon; Carbon Dioxide; Carbon Sequestration; Coal Ash; Diamines; Kinetics
PubMed: 30346754
DOI: 10.1021/acs.est.8b04253 -
Journal of Medicinal Chemistry Mar 2022To mitigate the systemic adverse effects of tofacitinib, 5-ASA-PABA-MAC and 5-ASA-PABA-diamine colon-specific delivery systems were constructed, and tofacitinib azo...
Discovery of a Colon-Targeted Azo Prodrug of Tofacitinib through the Establishment of Colon-Specific Delivery Systems Constructed by 5-ASA-PABA-MAC and 5-ASA-PABA-Diamine for the Treatment of Ulcerative Colitis.
To mitigate the systemic adverse effects of tofacitinib, 5-ASA-PABA-MAC and 5-ASA-PABA-diamine colon-specific delivery systems were constructed, and tofacitinib azo prodrugs and were synthesized accordingly. The release studies suggested that these systems could effectively release tofacitinib , and the 5-ASA-PABA-diamine system could successfully realize the colon targeting of tofacitinib . Specifically, compound displayed a 3.67-fold decrease of plasma AUC and a 9.61-fold increase of colonic AUC, compared with tofacitinib at a molar equivalent oral dose. Moreover, mouse models suggested that compound (1.5 mg/kg) could achieve roughly the same efficacy against ulcerative colitis compared with tofacitinib (10 mg/kg) and did not impair natural killer cells. These results demonstrated the feasibility of compound as an effective alternative to mitigate the systemic adverse effects of tofacitinib, and 5-ASA-PABA-MAC and 5-ASA-PABA-diamine systems were proven to be effective for colon-specific drug delivery.
Topics: 4-Aminobenzoic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis; Colitis, Ulcerative; Colon; Diamines; Drug Delivery Systems; Mesalamine; Mice; Piperidines; Prodrugs; Pyrimidines
PubMed: 35275619
DOI: 10.1021/acs.jmedchem.1c02166 -
Molecules (Basel, Switzerland) Oct 2022This paper presents the data of research studies on the mechanisms, kinetics and thermodynamics of decomposition of three high-energy compounds:...
This paper presents the data of research studies on the mechanisms, kinetics and thermodynamics of decomposition of three high-energy compounds: [1,2,4]triazolo[4,3-][1,2,4,5]tetrazine-3,6-diamine (TTDA), 3-amino-6-hydrazino[1,2,4]triazolo[4,3-][1,2,4,5]tetrazine (TTGA) and 3,6-dinitroamino[1,2,4]triazolo[4,3-][1,2,4,5]tetrazine (DNTT). The points of change of the reaction mechanisms under thermal effects with different intensities from 0.1 to 2000 s have been established. The values of activation and induction energies for the limiting stages of decomposition have been obtained. The formation of nanostructured carbon nitride (α-CN) in condensed decomposition products, cyanogen (CN) and hydrogen cyanide (HCN) in gaseous products have been shown. Concentration-energy diagrams for the reaction products have been compiled. The parameters of heat resistance and thermal safety proved to be: 349.5 °C and 358.2 °C for TTDA; 190.3 °C and 198.0 °C for TTGA; 113.4 °C and 114.1 °C for DNTT. The energy and thermodynamic properties have also been estimated. This work found the activation energy of the decomposition process to be 129.0 kJ/mol for TTDA, 212.2 kJ/mol for TTGA and 292.2 kJ/mol for DNTT. The average induction energy of the catalytic process (Ecat) for TTGA was established to be 21 kJ/mol, and for DNTT-1500-1700 kJ/mol. The induction energy of the inhibition process (Eing) of TTDA was estimated to be 800-1400 kJ/mol.
Topics: Hydrogen Cyanide; Thermodynamics; Kinetics; Hot Temperature; Heterocyclic Compounds; Diamines
PubMed: 36296568
DOI: 10.3390/molecules27206966 -
The Journal of Organic Chemistry Sep 2023Purine DNA represents an alternative pairing system formed by two purines in the base pair with the recognition elements of Watson-Crick DNA. Base functionalization of...
Purine DNA Constructs Designed to Expand the Genetic Code: Functionalization, Impact of Ionic Forms, and Molecular Recognition of 7-Deazaxanthine-7-Deazapurine-2,6-diamine Base Pairs and Their Purine Counterparts.
Purine DNA represents an alternative pairing system formed by two purines in the base pair with the recognition elements of Watson-Crick DNA. Base functionalization of 7-deaza-2'-deoxyxanthosine with ethynyl and octadiynyl residues led to clickable side chain derivatives with short and long linker arms. As complementary bases, purine-2,6-diamine or 7-deazapurine-2,6-diamine 2'-deoxyribonucleosides were used. 7-Deaza-7-iodo-2'-deoxyxanthosine served as a starting material for Sonogashira cross-coupling and the -nitrophenylethyl group for base protection. Phosphoramidite building blocks for DNA synthesis were prepared. Oligonucleotides containing single modifications or runs of three purine base pairs embedded in 12-mer Watson-Crick DNA were synthesized and hybridized with complementary strands with purine- or 7-deazapurine-2,6-diamine located opposite to the xanthine derivatives. The stability of base pairs was evaluated in a comparative study on the basis of DNA melting experiments and values. As 7-deazaxanthine and xanthine nucleosides form anionic forms at neutral pH, duplex stability became p-dependent, and the system with 7-deazapurine displayed a significant higher stability as that containing xanthine. Alkynyl side chains are well accommodated in the purine-purine helix. Click adducts with pyrene showed that short linker arms destabilize duplexes, whereas long linkers increase duplex stability. CD and fluorescence measurements provide further insights into purine-purine base pairing.
Topics: Base Pairing; Genetic Code; Purines; Xanthine; Diamines; Ions
PubMed: 37669119
DOI: 10.1021/acs.joc.3c01370 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2016Synthetic methods aimed at preparing peptides cross-linked by diaminodiacids remain an important chemical challenge. These cross-links are known to play a crucial role... (Review)
Review
Synthetic methods aimed at preparing peptides cross-linked by diaminodiacids remain an important chemical challenge. These cross-links are known to play a crucial role on the activity, structural stability, and folding of the host peptides and proteins. Recent developments in the syntheses of such systems have led to intriguing advances in the understanding of intermolecular side-chain cross-linking and the role that these structural motifs play in the biochemistry of proteins. Herein we provide an overview of the existing synthetic methodology that has been developed to effect protein cross-linking using diaminodiacids.
Topics: Amino Acid Sequence; Carboxylic Acids; Cross-Linking Reagents; Diamines; Peptides
PubMed: 26749083
DOI: 10.1002/chem.201503458 -
The Journal of Toxicological Sciences 2022Although both o-toluidine and o-anisidine are known as aromatic amines with bladder carcinogenicity, the specific metabolites involved in carcinogenesis are still...
Although both o-toluidine and o-anisidine are known as aromatic amines with bladder carcinogenicity, the specific metabolites involved in carcinogenesis are still unclear. Here, we examined the toxicological effects of head-to-tail dimers of o-toluidine and o-anisidine, 2-methyl-N-(2-methylphenyl) benzene-1,4-diamine (MMBD) and 2-methoxy-N-(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), respectively, in rats. Six-week-old male F344 rats were orally administered MMBD, MxMxBD, o-toluidine, and o-anisidine at a dose of 100 mg/kg/day for 28 days. Rats administered 400 mg/kg o-toluidine and 600 mg/kg/day o-anisidine were set as high-dose groups for comparison. Histopathology and immunohistochemistry for γ-H2AX, a DNA damage biomarker, and bladder stem cell markers, including aldehyde dehydrogenase 1A1 (ALDH1A1), were performed. MMBD and MxMxBD caused different toxicities than their monomers, inducing hepatotoxicity such as vacuolar degeneration but not splenic lesions due to methemoglobinemia. Bladder lesions, including urothelial hyperplasia, were observed in the high-dose o-toluidine and o-anisidine groups, whereas no obvious changes were induced in the low-dose groups or their dimers. Although γ-H2AX formation was significantly increased by o-toluidine and o-anisidine treatment, γ-H2AX formation did not differ among the MMBD, MxMxBD, and control groups. Notably, immunohistochemistry revealed marked increases in ALDH1A1 expression in the bladder urothelium of the MMBD and MxMxBD groups and in the o-toluidine and o-anisidine groups, suggesting that the two dimers may contribute to the bladder carcinogenic effects of o-toluidine and o-anisidine to some extent. The degrees of bladder lesions and γ-H2AX formation did not correlate with the amount of unchanged o-toluidine and o-anisidine in urine, indicating the presence of other metabolites responsible for these findings.
Topics: Rats; Male; Animals; Rats, Inbred F344; Benzene; Administration, Oral; Diamines
PubMed: 36328536
DOI: 10.2131/jts.47.457 -
Dalton Transactions (Cambridge, England... Aug 2023The complex [PtCl(cyclohexane-1,2-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (, the histone deacetylase inhibitor...
The complex [PtCl(cyclohexane-1,2-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (, the histone deacetylase inhibitor 2-propylpentanoic acid or valproic acid, VPA, and the potential antimetastatic molecule 4-isopropenylcyclohexene-1-carboxylic acid or perillic acid, PA) in order to obtain a set of multiaction or multitarget antiproliferative agents. In addition to traditional thermal synthetic procedures, microwave-assisted heating was used to speed up their preparation. All Pt(IV) complexes showed antiproliferative activity on four human colon cancer cell lines (namely HCT116, HCT8, RKO and HT29) in the nanomolar range, considerably better than those of [PtCl(cyclohexane-1,2-diamine)], VPA, PA, and the reference drug oxaliplatin. The synthesized complexes showed pro-apoptotic and pro-necrotic effects and the ability to induce cell cycle alterations. Moreover, the downregulation of histone deacetylase activity, leading to an increase in histone H3 and H4 levels, and the antimigratory activity, indicated by the reduction of the levels of matrix metalloproteinases MMP2 and MMP9, demonstrated the multiaction nature of the complexes, which showed biological properties similar to or better than those of VPA and PA, but at lower concentrations, probably due to the lipophilicity of the combo molecule that increases the intracellular concentration of the single components (, [PtCl(cyclohexane-1,2-diamine)], VPA and PA).
Topics: Platinum; Prodrugs; Diamines; Valproic Acid; Colonic Neoplasms; Humans; Cell Line, Tumor; Histone Deacetylases; Cell Movement; Antineoplastic Agents
PubMed: 37530512
DOI: 10.1039/d3dt01876h -
Journal of Environmental Science and... Mar 2018A sensitive and specific method for the determination of propineb and its metabolites, propylenethiourea (PTU) and propylenediamine (PDA), using gas chromatography with...
Determination of propineb and its metabolites propylenethiourea and propylenediamine in banana and soil using gas chromatography with flame photometric detection and LC-MS/MS analysis.
A sensitive and specific method for the determination of propineb and its metabolites, propylenethiourea (PTU) and propylenediamine (PDA), using gas chromatography with flame photometric detection (GC-FPD) and LC-MS/MS was developed and validated. Propineb and its metabolite residue dynamics in supervised field trials under Good Agricultural Practice (GAP) conditions in banana and soil were studied. Recovery of propineb (as CS), PDA and PTU ranged from 75.3 to 115.4% with RSD (n = 5) of 1.3-11.1%. The limit of quantification (LOQ) of CS, PDA and PTU ranged from 0.005 to 0.01 mg kg, and the limit of detection (LOD) ranged from 0.0015 to 0.0033 mg kg. Dissipation experiments showed that the half-life of propineb in banana and soil ranged from 4.4 to 13.3 days. PTU was found in banana with a half-life of 31.5-69.3 days, while levels of PDA were less than 0.01 mg kg in banana and soil. It has been suggested that PTU is the major metabolite of propineb in banana. The method was demonstrated to be reliable and sensitive for the routine monitoring of propineb and its metabolites in banana and soil. It also serves as a reference for the detection and monitoring of dithiocarbamates (DTCs) residues and the evaluation of their metabolic pathway.
Topics: Agriculture; Chromatography, Gas; Chromatography, Liquid; Diamines; Food Analysis; Food Contamination; Fungicides, Industrial; Half-Life; Limit of Detection; Musa; Pesticide Residues; Reproducibility of Results; Soil Pollutants; Tandem Mass Spectrometry; Thiourea; Zineb
PubMed: 29227190
DOI: 10.1080/03601234.2017.1399765