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BMC Plant Biology Dec 2022Moringa concanensis Nimmo (MC), a plant that resembles Moringa oleifera Lam. (MO), has less scientific information but has traditionally been used as a medicinal plant....
BACKGROUND
Moringa concanensis Nimmo (MC), a plant that resembles Moringa oleifera Lam. (MO), has less scientific information but has traditionally been used as a medicinal plant. Moringa species have long been known for their medicinal qualities, which include antioxidant, anti-inflammatory, anticancer, and antihyperglycemic effects. We investigated the antidiabetic potential of MC and MO species in this study by using transcriptome profiling, metabolite analysis, and in vitro assay studies.
RESULTS
Our transcriptome analysis revealed the expression of enzymes involved in the biosynthesis of quercetin, chlorogenic acid, and benzylamine, all of which have previously been shown to have antidiabetic activity. We compared the expression patterns of five different tissues from MC and MO and it was found that the key enzymes involved in the biosynthesis of these compounds were highly expressed in leaf tissue. The expression estimated by MC transcriptome data in different tissues was verified using RT-qPCR analysis. The amount of these compounds was further quantified in the crude leaf extract of both species and found that MC had a higher abundance of quercetin and chlorogenic acid than MO. The crude leaf extract from both MC and MO were further tested in vitro, and the results demonstrated strong inhibitory activity for α-glucosidase and DPP-IV enzymes. Our findings suggest that compounds in leaf tissue, such as quercetin, benzylamine, and chlorogenic acid, could play a significant role in this antidiabetic activity. In addition, when comparing MO plants, we found that MC had a slightly higher effect in expression, abundance, and inhibitory activity.
CONCLUSIONS
This study presents the first report of MC transcriptome data, as well as a comparison of its anti-diabetic activity to MO. Our analysis discussed the significance of leaf tissue in antidiabetic activity compared to other tissues of both species. Overall, this study not only provides transcriptome resources for Moringa species, but also sheds light on antidiabetic potential of both species.
Topics: Moringa; Hypoglycemic Agents; Quercetin; Chlorogenic Acid; Gene Expression Profiling; Benzylamines; Plant Extracts
PubMed: 36460949
DOI: 10.1186/s12870-022-03938-6 -
Journal of Neural Transmission (Vienna,... 2007Amine oxidase substrates such as benzylamine and methylamine have been shown to stimulate glucose uptake by increasing the recruitment of the glucose transporter GLUT4... (Review)
Review
Amine oxidase substrates such as benzylamine and methylamine have been shown to stimulate glucose uptake by increasing the recruitment of the glucose transporter GLUT4 from vesicles within the cell to the cell surface. Inhibition of this effect by the presence of semicarbazide and catalase led to the suggestion that the process is mediated by the H(2)O(2) produced in the oxidation of these amines. Tyramine, which is a substrate for both MAO and SSAO, can also stimulate this process and in that case both MAO and SSAO inhibitors attenuate the effect. Benzylamine does not occur physiologically and tyramine is normally present in only very low amounts. We have suggested that adrenaline, which also stimulates glucose metabolism through adrenoceptors, may act as the physiological substrate for GLUT4 recruitment. It is a substrate for MAO but not SSAO. However, oxidation of adrenaline by MAO releases both H(2)O(2) and methylamine for further oxidation by SSAO. In order to gain a fuller understanding of this process we have performed simulation studies that may be used to assess the contributions of the amine oxidases to the process under a variety of conditions. The results are consistent with the experimentally observed behaviour. This approach not only helps to establish the feasibility of this process but also allows behaviour prediction and the identification of further experimental approaches.
Topics: Amine Oxidase (Copper-Containing); Animals; Benzylamines; Biological Transport; Epinephrine; Glucose; Glucose Transporter Type 4; Humans; Hydrogen Peroxide; Models, Biological; Monoamine Oxidase; Tyramine
PubMed: 17406961
DOI: 10.1007/s00702-007-0688-6 -
Combinatorial Chemistry & High... 2022Phencyclidine (PCP, I) and its substituted analogs are significant and broadly abused psychotomimetic drugs that affect the central nervous system. They possess many...
BACKGROUND
Phencyclidine (PCP, I) and its substituted analogs are significant and broadly abused psychotomimetic drugs that affect the central nervous system. They possess many pharmacological properties due to the presence of specific receptors in the brain.
AIMS AND OBJECTIVE
Methyl group, despite strong electron-donating and characters of dipole moments, was placed on various positions of phenyl and amine moieties of phencyclidine along with the substitution of benzylamine, piperazine, and aniline derivatives in place of piperidine ring of phencyclidine to create novel compounds of the core with analgesic properties.
MATERIALS AND METHODS
For evaluation of the analgesic activities of newly synthesized compounds, they were screened by tests of tail immersion (thermal) and formalin (chemical) pains. The obtained data with the control and PCP groups were also compared.
RESULTS
The outcomes indicated that some new compounds have more antinociceptive effects than PCP in tail immersion and formalin tests. In the tail immersion test, the methyl piperazine analog (III) shows more efficacy than others. In the formalin test, none of the compounds are as effective as phencyclidine at the earliest time-point, but compounds IV and V show effectiveness during the second stage of formalin pain.
CONCLUSION
It can be concluded that the methyl-piperazine analog of phencyclidine was the best candidate to decrease acute thermal pain, and benzylamine derivatives were suitable candidates to reduce chemical pains.
Topics: Amines; Analgesics; Aniline Compounds; Animals; Benzylamines; Formaldehyde; Mice; Pain; Phencyclidine; Piperazines
PubMed: 34610782
DOI: 10.2174/1386207325666211005155128 -
Expert Opinion on Pharmacotherapy Mar 2000Butenafine, a derivative of benzylamine with potent fungicidal activity is a new generation of antimycotic compound that has shown to be extremely effective against... (Review)
Review
Butenafine, a derivative of benzylamine with potent fungicidal activity is a new generation of antimycotic compound that has shown to be extremely effective against experimentally-induced tinea pedis in the guinea-pig, a situation that resembles synergetic pathology similar to that of tinea pedis in humans. Butenafine, (N-4-tert-butylbenzyl-N-methyl-1-naphthalenemethyl-amine hydrochloride) with a chemical structure and mode of action similar to those of the allylamines, demonstrates superior fungicidal activity in vitro against dermatophytes and superior fungistatic activity toward Candida albicans that of naftifine and terbinafine. In vitro, pharmacodynamic data has shown that the geometric mean of minimum inhibitory concentration values for butenafine were comparatively lower than those of naftifine and clotrimazole against clinical isolates for many dermatophytes. It inhibits sterol synthesis by blocking the squalene epoxidation stage in fungi. In phramacokinetic assessments butenafine achieves and maintains high concentrations and long retention time in skin, with associated anti-inflammatory activity in vivo. In controlled clinical trials when applied topically, butenafine appears to be well tolerated with a subjective mild burning sensation at the application site. There were no withdrawals from the study. Butenafine is sparingly soluble in water but readily soluble in methanol, ethanol, dichloromethane and chloroform. If incorporated properly in semisolid topical preparations, with a balanced vehicle, butenafine hydrochloride potentially exhibits as a promising alternative antimycotic agent for the treatment of tinea pedis.
Topics: Animals; Antifungal Agents; Benzylamines; Humans; Naphthalenes; Tinea Pedis
PubMed: 11249531
DOI: 10.1517/14656566.1.3.467 -
Archiv Der Pharmazie May 1993Synthesis and testing for antimycobacterial properties (M. tuberculosis H 37 Ra, Middlebrook-7H9-broth) of 1-phenyl-1-alkylaminoalkanes, which differ from...
Synthesis and testing for antimycobacterial properties (M. tuberculosis H 37 Ra, Middlebrook-7H9-broth) of 1-phenyl-1-alkylaminoalkanes, which differ from antimycobacterial N-alkylbenzylamines by an additional alkyl chain in alpha-position, is described. By variation of both alkyl chains and introduction of one or two Cl-substituents in the aromatic ring the activity increases up to an optimum within the homologous series. Overstepping optimal lipophilicity or ramification of the alkyl chains decrease activity.
Topics: Antitubercular Agents; Benzylamines; Microbial Sensitivity Tests; Mycobacterium tuberculosis
PubMed: 8328884
DOI: 10.1002/ardp.19933260506 -
Molecular Pharmaceutics Jul 2022For most oral small-molecule projects within drug discovery, the extent and duration of the effect are influenced by the total clearance of the compound; hence,...
For most oral small-molecule projects within drug discovery, the extent and duration of the effect are influenced by the total clearance of the compound; hence, designing compounds with low clearance remains a key focus to help enable sufficient protein target engagement. Comprehensive understanding and accurate prediction of animal clearance and pharmacokinetics provides confidence that the same can be observed for human. During a MERTK inhibitor lead optimization project, a series containing a biphenyl ring system with benzylamine -substitution on one phenyl and nitrogen inclusion as the atom on the other ring demonstrated multiple routes of compound elimination in rats. Here, we describe the identification of a structural pharmacophore involving two key interactions observed for both the MERTK program and an additional internal project. Four strategies to mitigate these clearance liabilities were identified and systematically investigated. We provide evidence that disruption of at least one of the interactions led to a significant reduction in CL that was subsequently predicted from rat hepatocytes using in vitro/in vivo extrapolation and the well-stirred scaling method. These tactics will likely be of general utility to the medicinal chemistry and DMPK community during compound optimization when similar issues are encountered for biphenyl benzylamines.
Topics: Animals; Benzylamines; Biphenyl Compounds; Hepatocytes; Metabolic Clearance Rate; Models, Biological; Rats; c-Mer Tyrosine Kinase
PubMed: 35533086
DOI: 10.1021/acs.molpharmaceut.2c00014 -
The Journal of Physical Chemistry. A Aug 2014Phenylalkylamines of the general formula C6H5(CH2)nNH2 (n = 1-4) have been delivered to the gas phase as protonated species using electrospray ionization. The ions thus...
Phenylalkylamines of the general formula C6H5(CH2)nNH2 (n = 1-4) have been delivered to the gas phase as protonated species using electrospray ionization. The ions thus formed have been assayed by IRMPD spectroscopy in two different spectroscopic domains, namely, the 600-1800 and the 3000-3500 cm(-1) regions using either an IR free electron laser or a tabletop OPO/OPA laser source. The interpretation of the experimental spectra is aided by density functional theory calculations of candidate species and vibrational frequency analyses. Protonated benzylamine presents a relatively straightforward instance of a single stable conformer, providing a trial case for the adopted approach. Turning to the higher homologues, C6H5(CH2)nNH3(+) (n = 2-4), more conformations become accessible. For each C6H5(CH2)nNH3(+) ion (n = 2-4), the most stable geometry is characterized by cation-π interactions between the positively charged ammonium group and the aromatic π-electronic system, permitted by the folding of the polymethylene chain. The IRMPD spectra of the sampled ions confirm the presence of the folded structures by comparison with the calculated IR spectra of the various possible conformers. An inspection of the NH stretching region is helpful in this regard.
Topics: Aniline Compounds; Benzylamines; Cations; Computer Simulation; Hydrogen Bonding; Models, Chemical; Protons; Spectrophotometry, Infrared; Vibration
PubMed: 25061749
DOI: 10.1021/jp505037n -
ACS Synthetic Biology Sep 2021Benzylamine is a commodity chemical used in the synthesis of motion-sickness treatments and anticonvulsants, in dyeing textiles, and as a precursor to the high-energy...
Benzylamine is a commodity chemical used in the synthesis of motion-sickness treatments and anticonvulsants, in dyeing textiles, and as a precursor to the high-energy propellant CL-20. Because chemical production generates toxic waste streams, biosynthetic alternatives have been explored, recently resulting in a functional nine-step pathway from central metabolism (phenylalanine) in . We report a novel four-step pathway for benzylamine production, which generates the product from cellular phenylpyruvate using enzymes from different sources: a mandelate synthase (), a mandelate oxidase (), a benzoylformate decarboxylase (), and an aminotransferase (). This pathway produces benzylamine at 24 mg/L in 15 h (4.5% yield) in cultures of unoptimized cells supplemented with phenylpyruvate. Because the yield is low, supplementation with pathway intermediates is used to troubleshoot the design. This identifies conversion inefficiencies in the mandelate synthase-mediated synthesis of ()-mandelic acid, and subsequent genome mining identifies a new mandelate synthase ( sp. 1114.5) with improved yield. Supplementation experiments also reveal native redirection of ambient phenylpyruvate away from the pathway to phenylalanine. Overall, this work illustrates how retrosynthetic design can dramatically reduce the number of enzymes in a pathway, potentially reducing its draw on cellular resources. However, it also shows that such benefits can be abrogated by inefficiencies of individual conversions. Addressing these barriers can provide an alternative approach to green production of benzylamine, eliminating upstream dependence on chlorination chemistry.
Topics: Bacterial Proteins; Benzylamines; Carboxy-Lyases; Escherichia coli; Metabolic Engineering; Multigene Family; Oxidoreductases; Phenylpyruvic Acids; Transaminases
PubMed: 34491727
DOI: 10.1021/acssynbio.1c00021 -
Chemical Research in Toxicology Sep 2008Stable isotope-labeled compounds have been synthesized and utilized by scientists from various areas of biomedical research during the last several decades. Compounds... (Review)
Review
Stable isotope-labeled compounds have been synthesized and utilized by scientists from various areas of biomedical research during the last several decades. Compounds labeled with stable isotopes, such as deuterium and carbon-13, have been used effectively by drug metabolism scientists and toxicologists to gain better understanding of drugs' disposition and their potential role in target organ toxicities. The combination of stable isotope-labeling techniques with mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, which allows rapid acquisition and interpretation of data, has promoted greater use of these stable isotope-labeled compounds in absorption, distribution, metabolism, and excretion (ADME) studies. Examples of the use of stable isotope-labeled compounds in elucidating structures of metabolites and delineating complex metabolic pathways are presented in this review. The application of labeled compounds in mechanistic toxicity studies will be discussed by providing an example of how strategic placement of a deuterium atom in a drug molecule mitigated specific-specific renal toxicity. Other examples from the literature demonstrating the application of stable isotope-labeled compounds in understanding metabolism-mediated toxicities are presented. Furthermore, an example of how a stable isotope-labeled compound was utilized to better understand some of the gene changes in toxicogenomic studies is discussed. The interpretation of large sets of data produced from toxicogenomics studies can be a challenge. One approach that could be used to simplify interpretation of the data, especially from studies designed to link gene changes with the formation of reactive metabolites thought to be responsible for toxicities, is through the use of stable isotope-labeled compounds. This is a relatively unexplored territory and needs to be further investigated. The employment of analytical techniques, especially mass spectrometry and NMR, used in conjunction with stable isotope-labeled compounds to establish and understand mechanistic link between reactive metabolite formation, genomic, and proteomic changes and onset of toxicity is proposed. The use of stable isotope-labeled compounds in early human ADME studies as a way of identifying and possibly quantifying all drug-related components present in systemic circulation is suggested.
Topics: Alkynes; Animals; Benzylamines; Glutamic Acid; Humans; Isotope Labeling
PubMed: 18702535
DOI: 10.1021/tx800139z -
Biochimica Et Biophysica Acta Apr 2003Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. The combination of SSAO substrates and low concentrations of vanadate... (Review)
Review
Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. The combination of SSAO substrates and low concentrations of vanadate markedly stimulates glucose transport and GLUT4 glucose transporter recruitment to the cell surface in rat adipocytes by a mechanism that requires SSAO activity and hydrogen peroxide formation. Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase. Moreover, the acute administration of benzylamine and vanadate in vivo enhances glucose tolerance in non-diabetic and streptozotocin-induced diabetic rats and reduces hyperglycemia after chronic treatment in streptozotocin-diabetic rats. Based on these observations, we propose that SSAO activity and vanadate potently mimic insulin effects in adipose cells and exert an anti-diabetic action in an animal model of type 1 diabetes mellitus.
Topics: Adipocytes; Amine Oxidase (Copper-Containing); Animals; Benzylamines; Glucose; Humans; Hyperglycemia; Insulin; Insulin Receptor Substrate Proteins; Phosphatidylinositol 3-Kinases; Phosphoproteins; Phosphorylation; Rats; Semicarbazides; Signal Transduction; Vanadates
PubMed: 12686100
DOI: 10.1016/s1570-9639(03)00039-6