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Targeting the Nervous System
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Acetylcholine is synthesised from choline and acetyl coenzyme A in the nerve ending of the presynaptic nerve, catalysed by the enzyme choline acetyltransferase. Acetylcholine is incorporated into membrane-bound vesicles by means of specific carrier proteins. An action potential results in the opening of calcium ion channels and increases the intracellular Ca2+ concentration, which induces the vesicles to fuse with the cell membrane of the presynaptic nerve and release acetylcholine in to the synaptic cleft. The neurotransmitter crosses the synaptic cleft and binds to cholinergic receptors on the surface of the post-synaptic neurone. This has the effect of opening sodium ion channels in the post synaptic membrane and propagating the action potential in the post synaptic nerve; whereby the signal can carry on to its destination. The enzyme acetylcholinesterase hydrolyses acetylcholine into choline and ethanoic acid, which diffuse back into the presynaptic neurone. This breakdown prevents new action potentials from being continuously generated.
99mTc-labelled and pH-awakened microbeads entrapping surface-modified lipid nanoparticles for the augmented effect of oxaliplatin in the therapy of colorectal cancer
Published in Journal of Microencapsulation, 2020
Kuldeep Rajpoot, Sunil K. Jain
For preparing aliquots of different concentrations (10, 20, 40, and 80 µg/ml) of OP, a stock solution (1000 µg/ml) for each formulation (i.e. OP, SLN-OP, and FA-SLN-OP) containing drug (OP) was prepared. Then the well plates were treated with different concentrations and effect was recorded after 48 h. Formulations treated cultures were investigated for %cell viability of COLO-205 cells for 2 d. On the other hand, without treated culture was considered as a negative control. While Adriamycin (1.0 mM) treated culture containing cells were called as a positive control. The experiment was completed after adding cold trichloroacetic acid (TCA). The cells were fixed after adding TCA (50 µl, 30% w/v) and stored at 4 °C for 1 h. The plates were washed using tap water. The air-dried samples were added by 50 µl of sulforhodamine B (SRB) solution (0.40%, w/v in 1.0% ethanoic acid) and stored for the next 20 min. A trizma base (10 mM) was used to elute the bound stain from washed and air-dried samples. Then the absorbance was taken using a plate reader at wavelength 540 nm for all samples while the reference wavelength was kept at 690 nm. All experiments were conducted in three times. Eventually, the %control viability of cells was determined against control wells using the plate-by-plate method. Finally, half-maximal inhibitory concentration (IC50) of each tested formulation was determined. For this, a graph was drawn at different concentrations vs. %inhibition, then the value of IC50 was calculated from the slope of the graph.
Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Wagdy M. Eldehna, Sara T. Al-Rashood, Tarfah Al-Warhi, Razan O. Eskandrani, Amal Alharbi, Ahmed M. El Kerdawy
5-Bromobenzofuran-2-carbohydrazide 3 (0.3 g, 1.2 mmol) was added to a hot solution of equivalent amount of the appropriate isatin derivative (4a–g or 6a–h) in ethanol (15 ml) with catalytic amount of ethanoic acid. The reaction mixture was heated under reflux for 4–7 h with TLC monitoring, once the reaction completed, the reaction mixture was left for cooling then was filtered-off. The produced solid was washed with water, diethyl ether and recrystallized from dioxane/propanol mixture to produce target compounds 5a–g and 7a–h, respectively.
Advances in phosphoproteomics and its application to COPD
Published in Expert Review of Proteomics, 2022
Xiaoyin Zeng, Yanting Lan, Jing Xiao, Longbo Hu, Long Tan, Mengdi Liang, Xufei Wang, Shaohua Lu, Tao Peng, Fei Long
Metal oxide affinity chromatography (MOAC) is also a mainstream method used at this stage to enrich phosphopeptides that is unlike IMAC, which is based on the binding of phosphate groups to surface metal oxides in a bidentate manner [37] (Figure 1c). However, MOAC also has a relatively strong binding ability to nonphosphorylated peptides. In 2005, Larsen et al. [38] reported that the addition of the competitive binder 2,5-dihydroxybenzoic acid (DHB) to the buffer and a high concentration of trifluoroacetic acid (TFA) to the loading buffer significantly reduced the nonspecific binding of MOAC to nonphosphorylated peptides. Additionally, Thingholm and colleagues [39] found that loading peptides onto TiO2 resins with 2,5-dihydroxybenzoic acid (DHB), phthalic acid, lactic acid, or ethanoic acid reduced the nonspecific binding of MOAC to nonphosphorylated peptides and thus significantly improved selectivity. In addition to TiO2, metal oxides that can be used for MOAC include ZrO2 [40], Nb2O5 [41], and Fe3O4 [42]. Subsequently, Jabeen et al. reported that the rare earth metal oxides Sm2O3 [43], Gd2O3 [44], and La2O3 [45] could also be used for phosphorylated peptide enrichment and demonstrated that these rare earth metal oxides possess both high selectivity and sensitivity. Irfan’steam [46] utilized mesoporous materials to improve the enrichment of phosphopeptides greatly even at very low concentrations of β-casein. In 2020, Yu et al. [47] constructed Fe3O4 @ PDA @ PMAA @ PAMAM magnetic nanospheres by introducing polyamidoamine dendrimer (PAMAM) and polymethacrylic acid (PMAA) based on Fe3O4. Recently, Li et al. [48] used glutamate as a non-phosphopeptides scavenger to change the TiO2 loading buffer to obtain better phosphopeptide enrichment. In the specific enrichment of phosphotyrosine, Alhendal et al. [49] evolved novel core@shell particles (CSP) covering the metal oxides surface such as SiO2@Cr2O3-CSP, which achieved better linearity and reproducibility.