Synthesis and in vitro bioactivity evaluation of new glucose and xylitol ester derivatives of 5- aminosalicylic acid

New glucose and xylitol esters of 5-amino salicylic acid (5-ASA) were synthesized followed by evaluation of their in vitro antimicrobial, anti-cancer and anti-inflammatory activities. The results of the antimicrobial activity assessment revealed that the new final esters were more effective against Gram-negative as well as Gram-positive bacteria than the original drug. Furthermore, the new final products were confirmed by a cytotoxicity assay over HT-29 and 3T3 cell lines to be less toxic for normal cells compared to the initial drug. On the other hand, however, their suppressive effect against cancerous cells was somewhat lower. Meanwhile, the anti-inflammatory activity assay over a RAW264.7 macrophage cell line demonstrated that the NO inhibition activity of the conjugated drug to the previously mentioned saccharides, especially to glucose, has slightly improved compared to the non-conjugated drug. Finally, in silico screening was also performed in order to predict the potential interactions and binding energy of the novel products against cyclooxygenase (COX-1/COX-2) and lipoxygenase (5-LOX) proteins. Findings indicated that the new products had greater hydrogen bonds and binding affinities with the active sites of proteins towards 5-ASA

Enantioselectivity investigation of short polar peptides with different positions in the Michael reaction

This work reports the effectiveness of short polar peptides as asymmetric catalysts in Michael reactions to attain good yields of enantio- and diastereoselective isomers. In a comparison, glutamic acid and histidine produced greater ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric Michael addition reaction in water

Failure analysis method for enhancing circularity through systems perspective

Recently, a circular economy has attracted global attention as an approach for addressing material security and resource-efficiency issues. As our societies shift toward a circular economy, manufacturers need to not only produce environmentally conscious products but to also realize reliable systems that will ensure the closure of the loops of the products, components, and materials. To do so, early-stage design is crucial to effectively and efficiently detect possible failures and then take adequate countermeasures against them. Although a few methods of failure analysis have been proposed to address environmental issues, these methods have failed to consider the cause–effect relationships among failures. This will hinder manufacturers from identifying core problems that should be addressed in a given system. Therefore, this study extends failure mode and effect analysis, which is an engineering technique used to address potential failures, by addressing the entire system reliability in relation to circularity. As a result of a case study of a manufacturer aiming to increase circularity with their products on the market, we revealed that the proposed method is useful in the early stage of design to (a) identify failure modes where effects are largely given to or received from other failures, (b) develop countermeasures effectively by addressing root causes of failures, and (c) find an opportunity to collaborate with external actors

Clinical and molecular characterization of patients with YWHAG‐related epilepsy

Objective YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG-related epilepsy. Methods We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients. Results The phenotypic spectrum of YWHAG-related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2 years of life. Seizure freedom can be achieved in half of the patients (13/24, 54%). Intellectual disability (23/24, 96%), behavioral disorders (18/24, 75%), neurological signs (13/24, 54%), and dysmorphisms (6/24, 25%) are common. A genotype–phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand-binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p < .001). Significance This study suggests that pathogenic YWHAG variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype–phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling

Asymmetric aldol reactions catalyzed by the promiscuous aldo–ketoreductase enzyme

The promiscuous aldo–ketoreductase (AKR) enzyme is used as a sustainable biocatalyst for the first time to catalyze asymmetric aldol reactions in aqueous medium. The reactions between aromatic aldehydes and cyclic/acyclic ketones give the corresponding products in moderate yields and enantioselectivities in the presence of water. The influence of solvents, the mole ratio of substrates, and enzyme concentration are investigated. The mechanism of the AKR1A1-catalyzed aldol reaction is also discussed

Fabrication of Silver Nanoparticles Supported on Rice Straw: In Vitro Antibacterial Activity and its Heterogeneous Catalysis in the Degradation of 4-Nitrophenol

To investigate the influence of pH on the size and distribution of silver nanoparticles (Ag-NPs) as well as the antibacterial activity and catalytic performance of rice straw/silver nanocomposites (RS/Ag-NCs), Ag-NPs were synthesized on the surface of rice straw (RS) with various percentages of Ag-NPs (1.0, 5.0, 10.0, and 20.0 wt.%) under different temperatures and diverse pH values. The ultraviolet-visible spectroscopy of synthesized RS/Ag-NCs became noticeable with increased pH, and the peaks were blue-shifted to lower wavelengths. X-ray powder diffraction (PXRD) demonstrated the presence of pure Ag-NPs. Transmission electron microscopy (TEM) showed that the diameters of Ag-NPs on RS were between 7.78 and 2.84 nm at pH values of 8 to 10. The antibacterial activity of various sizes of Ag-NPs on RS was examined using Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) based on the well diffusion technique. Higher antibacterial activity was detected as the loading percentage of RS/Ag-NCs increased and particle size decreased. The superior catalytic performance of 20.0 wt.% RS/Ag-NCs was considered in a test reaction in 4-nitrophenol (4-NP) reduction in the presence of sodium borohydride (NaBH4) in an eco-friendly solvent at ambient temperature. The results represented the high-performance catalytic activity of 20.0 wt.% RS/Ag-NCs

Synthesis and in-vitro bioactivity evaluation of new galactose and fructose ester derivatives of 5-aminosalicylic acid

Inflammatory bowel disease (IBD) is the main risk factor for developing colorectal cancer which is common in patients of all ages. 5-aminosalicylic acid (5-ASA), structurally related to the salicylates, is highly active in the treatment of IBD with minor side effects. In this study, the synthesis of galactose and fructose esters of 5-ASA was planned to evaluate the role of glycoconjugation on the bioactivity of the parent drug. The antibacterial activity of the new compounds were evaluated against two Gram-negative and two Gram-positive species of bacteria, with a notable effect observed against Staphylococcus aureus and Escherichia coli in comparisons with the 5-ASA. Cytotoxicity testing over HT-29 and 3T3 cell lines indicated that the toxicity of the new products against normal cells was significantly reduced compared with the original drug, whereas their activity against cancerous cells was slightly decreased. The anti-inflammatory activity test in RAW264.7 macrophage cells indicated that the inhibition of nitric oxide by both of the monosaccharide conjugated derivatives was slightly improved in comparison with the non-conjugated drug

Fabrication, Characterization, and Functionalization of Single-Walled Carbon Nanotube Conjugated with Tamoxifen and Its Anticancer Potential against Human Breast Cancer Cells

In this experiment, we aimed to fabricate SWCNT conjugated with tamoxifen and evaluated its anticancer potential against human breast cancer cells (MCF-7). The results showed that SWCNT was synthetized successfully using chemical vapor deposition (CVD) method. The results of Raman spectroscopy, SEM, and TEM analyses confirmed the synthesis of highly pure SWCNT. The functionalization of SWCNT was performed by oxidizing of SWCNT, attachment of polyethylene glycol (PEG) to oxidized SWCNT, and attachment of azelaic acid to the polyethylene glycol group. As a result, the SWCNT with free functional carboxylic acid and hydroxyl groups (SWCNT-PEG) was developed. The SWCNT-PEG was then conjugated with tamoxifen (SWCNT-PEG-TAM). The FT-IR together with NMR results confirmed the conjugation of tamoxifen to functionalized SWCNT (SWCNT-PEG-TAM). The cytotoxic concentrations (CC50) of SWCNT-PEG, tamoxifen, and SWCNT-PEG-TAM were >100, 12.67±2.69, and 5.49±1.34μg/ml, respectively. Linking tamoxifen to functionalized SWCNT enhanced the cytotoxic action of tamoxifen against breast cancer cells up to 2.3 times. The results of the morphological examination and caspase-3 activity confirmed the higher cytotoxic action of SWCNT-PEG-TAM as compared to free tamoxifen. The results obtained in this study indicated that this delivery system enhanced the therapeutic effects and anticancer potential of tamoxifen against human breast cancer cells