Search

In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance, as their detection is difficult or expensive using available methods such as HPLC or LC-MS. DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Herein, a method for quantifying small molecules using a ready-to-use sequencing platform is described. Taking ethanolamine as an example, a strand displacement assay is developed in which the target-binding aptamer is displaced from the surface of magnetic particles by ethanolamine. Non-displaced aptamer and thus the ethanolamine concentration are detected by the nanopore system and can be quantified in the micromolar range using our in-house developed analysis software. This method is thus the first to describe a label-free approach for the detection of small molecules in a protein nanopore system. A new approach for small molecule detection using a ready-to-use protein nanopore platform was designed. Using ethanolamine as an example, a strand displacement assay with magnetic beads and a target-binding aptamer was developed and optimized. The nanopore signals can be analysed with our in-house developed software. Ethanolamine was successfully detected quantitatively in the micromolar range. [Display omitted] • Small molecules are detected using a protein nanopore system. • Ethanolamine is quantified using its binding aptamer in the micromolar range. • Ethanolamine aptamer is displaced from magnetic beads and measured on nanopores. [ABSTRACT FROM AUTHOR]

Abstract Incensole and its acetate have shown anti-inflammatory and anti-depression activities due to their ability to activate ion channels in the brain to alleviate anxiety or depression. The natural occurrence of these two structurally and medicinally fascinating 14-membered diterpenoids was reported mainly from the genus Boswellia. Incensole and incensole acetate were detected in and isolated from both essential oils and resins of frankincense. One total synthesis was reported for incensole. Both incensole and its acetate served as precursors for several synthetic transformations. Given the fact that no specific enzymes were isolated from Boswellia trees, the major sources for incensole and incensole acetate, the biosynthetic pathway of these two compounds was only speculated. Recent studies on incensole and incensole acetate including ours have revealed another secret of the ancient drug. Understanding their mode of action will open a door in modern neurobiology and provides new insights on the mysterious diseases of the nervous system. This review interpretatively discusses the natural existence of incensole and incensole acetate, the variation of their percentages in different Boswellia species and other sources, their synthetic modifications, their biosynthesis and their therapeutic potential. Graphical abstract Image 1021822 Highlights • Incensole and its acetate are structurally and medicinally fascinating 14-membered diterpenoids and their content varies from one species to another. • Genus Boswellia is a major source for incensole and incensole acetate where both can be considered as biomarkers for Boswellia papyrifera. • A few synthetic derivatives and one total synthesis were reported for incensole. • Exceptional anti-inflammatory and anti-depression activities were reported for incensole and its acetate but their bioavailability should be improved. • Methods for increasing the natural abundance of incensole and its acetate should be solicited to further explore their therapeutic potential. [ABSTRACT FROM AUTHOR]

In the course of our continuing exploration for novel bioactive lead compounds (s) from the species Boswellia , we have recently reported incensole derivatives isolated from Boswellia papyrifera Hochst. Given the known antidepressant-like effects of incensole and incensole acetate, we herein present that the low dose intraperitoneal administration of incensole derivatives, namely, incensfuran and incensone, showed significant antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST). Furthermore, these compounds were evaluated for their anxiolytic potential in the elevated plus maze (EPM) and light dark box (LDB) tests and anticonvulsant effects in pentylenetetrazole (PTZ)-induced seizure tests. In the EPM test, administration of these compounds led to dose-dependent increases in open arm entries and in the time spent in EPM open arms. Similar results were obtained in the LDB test, wherein compounds these caused significant increases in the number of transitions between lit and dark compartments and the time spent in the lit compartment. The anxiolytic-like effects in the EPM were not reversed by pretreatment with flumazenil, whereas PTZ and bicuculline (BIC) completely abolished the anxiolytic effects, showing the involvement of the non-benzodiazepine binding sites of GABA A receptors. All four compounds induced significantly elevated brain GABA levels, indicating the involvement of a GABAergic mechanism. Additionally, molecular docking was conducted to elucidate the mode of action for the anxiolytic and anticonvulsant effects of these derivatives. Moreover, these compounds also possess drug-like properties and excellent ADMET profiles. Image 1 • The antidepressant-like effect of incensole and its derivatives (1–4) were evaluated. • Compounds 1–4 were evaluated for their anxiolytic and anticonvulsant effects. • Compounds 1 – 4 significantly increase brain GABA levels, indicating the involvement of a GABAergic mechanism. • Molecular docking was carried out to elucidate the mode of action for the anxiolytic and anticonvulsant effects of these derivatives. [ABSTRACT FROM AUTHOR]

In the current investigation, 5- epi -incensole (3) and 5- epi -incensole acetate (5) were synthesized from the most potent anti-depressant constituents incensole (1) and incensole acetate (2) of Boswellia papyrifera Hochst. The resulting compounds were evaluated for their ability to ameliorate depressive symptoms in forced swim test (FST) and tail suspension test (TST) in chronic unpredictable mild stress (CUMS) induced depression paradigm. The results demonstrated that compounds 3 and 5 at the doses of 1 and 3 mg/kg administered for 28 days, significantly reduced the immobility time in FST and TST and were devoid of any effect on locomotor activity in the open field test (OFT). Both compounds 3 and 5 also reversed CUMS-induced reduction in the weight of animals and aversion in sucrose preference. The tested compounds also inhibited Monoamine oxidase-A (MAO) enzyme and increased the levels of brain noradrenaline (NA) and 5-Hydroxytryptamine (5-HT), decreased plasma corticosterone and pro-inflammatory cytokines including TNF-α, IL-6 in hippocampal homogenates. Compounds 3 and 5 also significantly reduced the increased lipid peroxidation and nitrite levels; decreased glutathione levels, and catalase activities in mice undergoing CUMS protocol. The binding mode of compounds 3 and 5 was predicted at the monoamine oxidase substrate binding site by molecular docking having docking scores of > −6 kcal/mol. Taken together these data revealed that compounds 3 and 5 exerted antidepressant-like effects in chronic unpredictable mild stress-induced depression paradigm and are likely mediated via modulating the central oxidative stress, MAO-A activity with a consequent increase in brain NA and 5-HT levels in inflammatory pathways. • 5-epi-incensole (3) and 5-epi-incensole acetate (5) were synthesized from potent anti-depressant constituents incensole (1) and incensole acetate (2) of Boswellia papyrifera. • Both compounds 3 and 5 were evaluated in forced swim test and tail suspension test in chronic unpredictable mild stress. • These compounds also inhibited Monoamine oxidase-A (MAO) and decreased the levels of plasma corticosterone and pro-inflammatory cytokines including TNF-α, IL-6 in hippocampal homogenates. • Compounds 3 and 5 also significantly reduced lipid peroxidation and nitrite levels, decreased glutathione levels and catalase [ABSTRACT FROM AUTHOR]

Palladium-catalyzed chemoselective and regioselective cross-coupling reactions of 2,3-dichloro-1,4-(trifluoromethanesulfonyloxy)naphthalene with aryl boronic acids selectively afforded a variety of mono-, di-, and tetraphenylnaphthalenes. These reactions proceeded with excellent chemoselectivity in favor of the triflate functional group at the C-1 and C-4 positions of naphthalene. [ABSTRACT FROM AUTHOR]

β -Boswellic acid (β -BA) and 11-keto- β -boswellic acid (β -KBA) are crucial bioactive compounds, mostly isolated from frankincense. These compounds are known for their potent anticancer and anti-inflammatory activities. Herein, we have explored the complete anti-diabetic potential of β -BA and β -KBA with detailed parameters. This research revealed that treatment with β -BA and β -KBA at a dose of 1, 2, and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and specifically the concentration of blood glucose level (BGL) in diabetic animals, which indicated that the β -BA and β -KBA possess strong anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the antioxidant effects. The biochemical analysis revealed that these compounds improve an abnormal level of several biochemical parameters like serum lipid values including total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) to a normal level and the high-density lipoprotein cholesterol level (HDL-C). To understand the mechanism of action of β -BA and β -KBA, their most probable biological targets were searched through the inverse docking approach. Our computational analysis reflects that among other probable targets, the Dipeptidyl peptidase 4 (DPP-4) enzyme could be one of the possible binders of β -BA and β -KBA to produce their anti-diabetic activities. These in-silico results were validated by an in-vitro experiment. It indicates that the anti-diabetic effects of β -BA and β -KBA are produced by the inhibition of DDP-4. Thus, these anti-diabetic, antioxidant, and anti-hyperlipidemic effects of β -BA and β -KBA suggest these compounds as potential therapeutics for diabetic conditions. [Display omitted] • β -BA and β -KBA were isolated from oleo-gum resins of B. sacra. • In-vivo antidiabetic potential of β -BA and β -KBA was evaluated in STZ-induced high-fat diet diabetes mellitus. • β -BA and β -KBA reduced the hyperglycemia condition and improved biochemical parameters like lipid profile. • Both compounds possess in-vitro antioxidant potential. • DPP-4 was identified as prominent target for β -BA and β -KBA by in-silico target fishing. • In-silico results were validated by in-vitro assay of DPP-4. [ABSTRACT FROM AUTHOR]