The S. aureus bacterium is surrounded by capsular polysaccharides. These capsular polysaccharides are important in the pathogenesis of staphylococcal infection. There are 11 serotypes of capsular polysaccharides that have been identified, and a majority of strains express capsular polysaccharides type 5 (CP5) or 8 (CP8). The main focus of this review is to describe recent advances in the area of the chemical synthesis of monosaccharide components of S. aureus CP, oligosaccharide assembly and functionalization. Chemical routes to obtain oligosaccharides derived from CP1, CP5 and CP8 represent a compendium of modern classics of the total synthesis of challenging glycan sequences.
26 February 2021 in Organic & Biomolecular Chemistry
Reported herein is a new method for a highly effective synthesis of β-glycosides from mannuronic acid donors equipped with the 3-O-picoloyl group. The stereocontrol of glycosylations was achieved by means of the H-bond-mediated aglycone delivery (HAD). The method was utilized for the synthesis of a tetrasaccharide linked via β-(1 → 3)-mannuronic linkages. We have also investigated 3,6-lactonized glycosyl donors that provided moderate to high β-manno stereoselectivity in glycosylations. A method to achieve complete α-manno stereoselectivity with mannuronic acid donors equipped with 3-O-benzoyl group is also reported.
Charantin is a mixture of β-sitosterol and stigmastadienol glucosides, which effectively lowers high blood glucose. Novel molecularly imprinted polymers coated magnetic nanoparticles (Fe3O4@MIPs) and filter paper (paper@MIPs) were synthesized by sol-gel polymerization to selectively extract charantin. β-sitosterol glucoside was selected as a template for imprinting a specific recognition owing to its larger molecular surface area than that of 5,25-stigmastadienol glucoside. Factorial designs were used to examine the effects of the types of porogenic solvents and cross-linkers on the extraction efficiency and imprinting factor before investigating other factors (for example, amounts of template and coated MIPs, and types of substrates for MIP immobilization). Compared to traditional liquid–liquid extraction, the optimal Fe3O4@MIP-based dispersive micro-solid phase extraction and paper@MIP extraction provided excellent extraction efficiency (87.5 ± 2.1% and 85.0 ± 2.9%, respectively) and selectivity. Charantin was well separated, and a new unidentified sterol glucoside was observed using the developed high-performance liquid chromatography with diode-array detection (Rs ≥ 2.0, n > 16,400). The developed methods were successfully utilized to extract and quantify charantin from M. charantia fruit powder and herbal products. Moreover, these methods are rapid (<10 min), inexpensive, simple, reproducible, and environmentally friendly.
This study involved designing, synthesizing, and evaluating the protective potential of compounds on microglial cells (BV-2 cells) and neurons (SH-SY5Y cells) against cell death induced by Aβ1–42. It aimed to identify biologically specific activities associated with anti-Aβ aggregation and understand their role in oxidative stress initiation and modulation of proinflammatory cytokine expression. Actively designed compounds CE5, CA5, PE5, and PA5 showed protective effects on BV-2 and SH-SY5Y cells, with cell viability ranging from 60.78 ± 2.32% to 75.38 ± 2.75% for BV-2 cells and 87.21% ± 1.76% to 91.55% ± 1.78% for SH-SY5Y cells. The transformation from ester in CE5 to amide in CA5 resulted in significant antioxidant properties. Molecular docking studies revealed strong binding of CE5 to critical Aβ aggregation regions, disrupting both intra- and intermolecular formations. TEM assessment supported CE5's anti-Aβ aggregation efficacy. Structural variations in PE5 and PA5 had diverse effects on IL-1β and IL-6, suggesting further specificity studies for Alzheimer's disease. Log P values suggested potential blood–brain barrier permeation for CE5 and CA5, indicating suitability for CNS drug development. In silico ADMET and toxicological screening revealed that CE5, PA5, and PE5 have favorable safety profiles, while CA5 shows a propensity for hepatotoxicity. According to this prediction, coumarin triazolyl derivatives are likely to exhibit mutagenicity. Nevertheless, CE5 and CA5 emerge as promising lead compounds for Alzheimer's therapeutic intervention, with further insights expected from subsequent in vivo studies.
Coumarin-based molecular hybrids provide a framework for examining how structural changes influence cellular responses. This study compared four hybrids and three reference compounds across ten human cancer cell lines, with the lead hybrid also tested in non-cancerous Beas-2B cells, followed by functional assays and quantitative expression proteomics in HT-29 cells. Of 70 compound–cell-line combinations, the ferulic ester hybrid (FEC) was the only compound to yield a reproducibly measurable IC50 within the primary screening range, reaching 42.8 ± 4.7 µM in HT-29 cells. Replacing the ferulic moiety or the ester linkage reduced activity within this series. HCT116 cells did not reach 50% inhibition at up to 100 µM. Basal PPARγ abundance did not consistently explain sensitivity across the panel. FEC reduced metabolic activity and colony formation, whereas annexin V/propidium iodide analysis showed a smaller apoptotic response. Proteomics identified coordinated decreases in DNA replication and translation proteins and a modest increase in endoplasmic reticulum protein-folding enzymes. These findings support a structure-dependent and cell-context-dependent antiproliferative response despite moderate potency.