13C NMR Research Articles

2-(Heptylthio)pyrimidine-4,6-diamine

Thiopyrimidines represent one of the most active classes of compounds, possessing a wide spectrum of biological activities. Herein, we report the synthesis of 2-(heptylthio)pyrimidine-4,6-diamine (HPDA) via S-alkylation. The structure of HPDA was elucidated using 1H and 13C nuclear magnetic resonance (NMR), heteronuclear multiple bond correlation (HMBC), high resolution mass (HRMS), and infrared (IR) spectroscopies.

Amidated and Aminated PMSSO-Hydrogels as a Promising Enzyme-Sensitive Vehicle for Antianemic Drugs

In this study, we report the synthesis and characterization of aminated poly(methyl silsesquioxane)-based hydrogels ((AP/MS)SO-hydrogels) as potential enzyme-sensitive vehicles for antianemic drugs. The hydrogels were synthesized via sol–gel polymerization and functionalized with amine groups. Characterization techniques included Congo red assay, Brunauer–Emmett–Teller (BET) surface area analysis, scanning electron microscopy, elemental analysis, 13C NMR, 29Si NMR, and ATR-FTIR spectroscopy and microscopy of hydrogels. The sorption of ferric chloride and ferrous D-gluconate, as well as complexes of ferrous D-gluconate with HPCD, was evaluated. Crosslinking of the gel with bifunctional agents was performed to create a new amide enzyme-sensitive bond, followed by infrared characterization of the crosslinked product. Trypsin-mediated degradation studies demonstrated the sensitivity of the hydrogel to enzymatic cleavage under model conditions. Iron release experiments in gastric and intestine-simulating media confirmed prolonged release. Overall, our findings suggest that aminated PMSSO-hydrogels hold promise as versatile and biocompatible carriers for targeted delivery of antianemic agents, warranting further exploration in preclinical and clinical applications.

Biocatalytic conversion of microalgal biomass to biodiesel: optimization of growth conditions and synthesis of CaO bionanocatalyst from Monoraphidium sp. NCIM 5585

Microalgal feedstock is a potential source for biodiesel production that addresses the challenges of fuel security and sustainable agriculture. This study aims to maximize biomass yield and lipid accumulation for freshwater microalga Monoraphidium sp. NCIM 5585 and utilize it for biodiesel production, contributing to the development of biocatalysis-based biofuels. Independent optimization studies were conducted to investigate critical growth parameters, viz., light intensity, photoperiod, and NaNO3 concentration. The study showed highest biomass productivity of 51.75 ± 1.9 mg/L.d and lipid content of 47.3 ± 0.02% (w/w) at 40 µmol/m2/s light intensity, 16 h L:08 h D photoperiod, and 0.25 g/L NaNO3. Further, a novel CaO bionanocatalyst was synthesized using residual microalgal biomass and characterized using SEM, EDX, FT-IR, and XRD. The characterization results from SEM and EDX confirmed the structural and elemental composition of bionanocatalyst with Ca and O as main elements. XRD revealed the crystalline nature of CaO with particle size of 17.83 nm. 86.5 ± 0.65% (w/w) FAME was obtained using the synthesized catalyst and was characterized using 1H NMR, 13C NMR and GC-MS. This study demonstrates the potential of Monoraphidium sp., optimized growth conditions and the significance of reusability of residual microalgal biomass as catalyst for sustainable biodiesel production, offering a promising solution for fuel security and biotechnology applications.

(1S,1′S)-2,2′-(Benzylazanediyl)bis(1-((3aR,4R,6aR)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)ethan-1-ol)

(1S,1′S)-2,2′-(Benzylazanediyl)bis(1-((3aR,4R,6aR)-2,2-dimethyltetrahydrofuro [3,4 d][1,3]dioxol-4-yl)ethan-1-ol), presenting a tertiary β-aminodiol moiety, was synthesized in 72% yield in a one-step reaction from an aminolysis of an isosorbide-derived oxirane with benzylamine. This β-aminodiol was fully characterized by 1H and 13C NMR and HRMS analyses.

HSQCid: A Powerful Tool for Paving the Way to High-Throughput Structural Dereplication of Natural Products Based on Fast NMR Experiments.

Structural dereplication is an essential step in the study of natural products (NPs). The number of discovered NPs is so large that efficient dereplication is highly desirable. NMR spectroscopy is still the gold standard for structural identification. 13C NMR spectrum is an effective molecular fingerprint, but their acquisition is time-consuming, especially for mass-limited NPs. Several alternative methods or tools have been proposed but have never reached general use for some reasons. Here, a new artificial intelligence tool, HSQCid, using contrastive learning between 1H-13C HSQC spectra and structures, is proposed for effective structural identification. Two structure encoders are compared, and the graph neural network is preferred over the Transformer. In this way, 80% and 20% of about 400,000 predicted data could be used for training and testing, respectively. Besides, with 17,971 experimental data as external test data, the top-1 and top-10 accuracies reach 74.5% and 94.8%, respectively. Top-1 accuracy increases by at least 12% when combined with other easily obtainable structure features, such as the total number of hydrogens connected to carbons from 1H NMR spectra. Further data analysis shows that the filters by structure features nearly eliminate the influence (>10%) of the difference between predicted and experimental data. Surprisingly, the influence of the number or the ratio of nonprotonated carbons on the identification accuracy is only significant in specific and rare cases (2.65%). Furthermore, the benchmark method, which matches 13C peaks, is compared and is markedly inferior to the proposed method, with or without structural features. The HSQCid code is available online. It is believed that HSQCid contributes to paving the way for high-throughput or highly effective structural dereplication of NPs.

Bioactive Polyphenolic and Terpenoid Compounds from Stem Bark and Flowers of Terminalia brownii

Introduction Terminalia brownii Fresen (Combretaceae) extensively used in Eastern, Southern, and Western Africa herbal remedies in treatment of variety of diseases including liver cirrhosis. Bioassay – guided fractionation was used to isolate the compounds responsible for these actions. Aim of the Study The study sought to extract, characterize and determine the antimicrobial activities of the components of the commonly used stem bark and hitherto uninvestigated regeneratable flowers of T.brownii. Materials and Methods Column chromatography was used to fractionate and isolate the compounds followed by thin layer chromatography. The isolates were structurally elucidated using FTIR, 1H NMR, 13C NMR and HRESI-MS spectral data. The isolated compounds' antimicrobial activities were evaluated against Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Results Bioassay – guided fractionation of methanol and 50% dichloromethane: methanol extracts of Terminalia brownii stem bark and flowers yielded seven known metabolites; termiglaucescin (1), arjunglucoside-I (2), sericoside (3), 23-galloyl arjungenin (4), 28-O-β-D-glucopyranosyl-2,3,6-trihydroxy-23-galloylolean-12-dien-28-oate (5), 3,3',4',5-tetrahydroxy-7-methoxyflavone (9), 3,3',4',5,7-pentahydroxyflavone (10) and three new metabolites: 1,4,7-tri-O-galloyl hept-6-deoxyheptose (6), 1,2,4-tri-O-galloyl-8,9-dideoxynonose (7), Rhamnetin-3-O-(2,3,6-trigalloyl)-β-D-glucopyranoside (8). Among these molecules, compound (6) was extremely potent toward E. coli (16.5±0.7 mm) while (1) showed substantial inhibitory effects on Candida albicans (16.0±5.7 mm). Compounds 6, 7, 8, 9, and 10 were extracted and identified for the first time from 50% dichloromethane/methanol flower extract. The extract yielded three novel bioactive compounds (6, 7 and 8) that shown substantial activity on P.aeruginosa, E. coli, C. albicans, S. aureus. Conclusion For the first time, the results of this investigation demonstrate that flower extract possess strong antibacterial and antifungal qualities, akin to those of stem bark extract. As a result, more environmentally friendly flower extracts should be considered for treatment of bacterial and fungal infection.

One pot pyridinium ylide assisted tandem reaction for the diastereoselective synthesis of trans-2,3-dihydrofuran-chromone conjugate

An efficient synthetic procedure for the preparation of novel fused 2,3- dihydrofurans-chromone conjugates was developed with the assistance of in situ generated pyridinium ylide. Pyridine, 3-formylchromone, 1,3-diketo and phenacyl bromide with triethylamine acting as a catalyst, initiated a sequential one-pot, two-step tandem reaction that went smoothly in aqueous media.1H and 13CNMR spectroscopy and single-crystal analysis demonstrated the diastereoselective synthesis of trans-2,3-dihydrofurans.

Pharmacophore Recombination Design, Synthesis, and Bioactivity of Ester-Substituted Pyrazole Purine Derivatives as Herbicide Safeners.

Mesosulfuron-methyl, an acetolactate synthase (ALS) inhibitor primarily applied to wheat and rye, can injure or even kill wheat crops. Herbicide safeners can improve the herbicide resistance of crops without reducing the herbicidal effect on targeted weed species. Herein, we present a series of pyrazole purine derivatives with the primary structure of the natural product cytokinin and commercialized safener mefenpyridyl, designed using the pharmacophore recombination method. The title compounds were synthesized and characterized using infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. A bioactivity assay proved that most of the target compounds can reduce the wheat phytotoxicity of mesosulfuron-methyl. Measurements of chlorophyll and glutathione contents, along with other enzyme activity assays, confirmed that compounds I-15 and I-13 exhibit higher safety activities compared with the mefenpyr-diethyl safener. Molecular structure comparisons demonstrated that I-15 is more readily absorbed and disseminated through the crop than the commercialized safener mefenpyr-diethyl. Molecular docking models and molecular dynamics simulations elucidated the protective mechanism of safeners; specifically, compound I-15 competitively binds to the ALS active site with mesosulfuron-methyl. The current study reveals the potential of pyrazole purine derivatives in the future discovery of novel herbicide safeners.

Form-Factor Control of Alginate Aerogels Via Thixotropic Sols: From Monoliths to Fibers to Films.

Producing homogeneous alginate aerogel monoliths is challenging due to the uncontrollably fast gelation of sodium alginate (NaALG) solutions, which is typically induced with metal ions. This issue is overcome by decoupling molding from gelation. Aqueous NaALG solutions are first converted into thixotropic liquids via in situ acidification with acetic acid (AcOH) generated gradually through the hydrolysis of acetic anhydride (Ac2O), thus, providing time for casting in molds. The resulting solid-like thixotropic liquids are rigidized into wet gels conforming to the molds by a membraneless dialysis process via nonsolvent-induced phase separation, treatment with strong acids (HCl), or aqueous metal ion solutions (Ca2+, Cu2+, Fe3+, Ni2+, Ag+, Au3+). The thixotropic nature of the NaALG/Ac2O mixtures enables extrusion into fibers or spreading into films, followed by rigidization using the same methods. Wet gels in monolithic, fibrous, or film form were dried into aerogels with supercritical fluid (SCF) CO2. All aerogels were characterized by SEM, N2-sorption porosimetry, IR spectroscopy, solid-state CP MAS 13C NMR, and elemental analysis. Oscillatory rheology tracked the transition of NaALG to thixotropic liquids during Ac2O and AcOH titrations run in parallel. Thixotropic liquids from both titrations were rigidized with the nonsolvent-induced phase separation method and were processed into aerogels establishing that AcOH from the hydrolysis of Ac2O converts up to ∼30% mol/mol of NaALG to alginic acid (ALGH). Conversion of the remaining NaALG in thixotropic liquids to ALGH (>95% mol/mol) requires a strong acid (HCl), while rigidization with metal ions just replaces residual Na. Dynamic mechanical analysis (DMA) showed nearly identical storage moduli (E') for wet gels and aerogels, confirming that the solid network is formed during the rigidization step and is unaffected by subsequent processing. Notably, elemental analysis, porosimetry, and DMA data indicated that gels rigidized with Fe3+ included a secondary network, which, based on literature Mössbauer reports, is assigned to sol-gel-derived iron oxide.

Thiol-maleimide click reaction-driven imprinted polymer for chiral resolution of indoprofen.

Indoprofen (INP) comprises two enantiomers, R- and S-, whose high pharmacological efficacy is realized only in the case of the separated enantiomers. A newly synthesized poly(acrylonitrile-co-divinylbenzene) (PANB)-based sorbent with selective affinity to the S-enantiomer of INP was applied to separate INP racemate. The synthesis was performed by suspension polymerization with low-crosslinked PANB microparticles and by reaction of the inserted nitriles with 1-amino-1H-pyrrole-2,5‑dione (Ma-NH2). The cationic maleimide-hydrazidine was then attached to the polymer particles, followed by its loading with anionic S-INP. In the post-crosslinking, ethane-1,2-dithiol (ETH) was used as a crosslinker through a thiol-maleimide click reaction, which attached the ETH to the maleimide groups in Ma-P. Acidic elution released S-INP enantiomers through specific receptor sites formed in the imprinted polymer particles, S-INP-P. Characterization of the polymers was done by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (13C NMR), and X-ray diffraction (XRD) while the surface morphology of the sorbents was investigated by scanning electron microscope (SEM). Optimum conditions for the enantioselective adsorption indicated that at pH 7, 285 mg/g of S-INP can be extracted. The chiral separation of the INP racemate led to an ee of 85% for R-INP in the first run and 97% for S-INP during elution.

Investigation on Diabetes and Mechanism of Thiadiazole–Schiff Base as Therapeutic Hybrid: Enzyme Activity and Molecular Docking Studies

AbstractIn an approach to combat diabetes mellitus, a widely spread noncommunicable disease (NCDs), a novel series of compounds (1–18) containing substituted thiadiazole bearing Schiff base derivative was synthesized and evaluated against enzymes causing diabetes mellitus. The results confirm that most of the compounds were found active and exhibit excellent biological activity as compared to the standard drug acarbose. Their minimal inhibitory concentrations for both enzymes lie in a range between 18.10 ± 0.30 and 2.10 ± 0.30 µM for α‐amylase and 19.20 ± 0.30 µM and 2.70 ± 0.80 µM for α‐glucosidase in contrast with the reference drug having IC50 of 4.30 ± 0.40 and 5.10 ± 0.70 µM. The most active analogs were found to be 2, 4, 7, 9, and 15, which displayed few‐fold higher potency than the control drug. Structural evaluation was conducted using various spectroscopic techniques such as 1H NMR, 13C NMR and HREIMS for all the synthesized derivatives, and in silico molecular docking studies of all the active analogs confirms the interactions between ligand and binding proteins.

Synthesis and diverse crystal packing in o-, m- and p-bis(carbonylthioureido)benzenes containing bisferrocenes.

Three bisferrocene-based bis(acylthiourea) positional isomers, namely, 1,2-bis(ferrocenylcarbonylthioureido)benzene (1), 1,3-bis(ferrocenylcarbonylthioureido)benzene (2) and 1,4-bis(ferrocenylcarbonylthioureido)benzene (3), all [Fe2(C5H5)2(C20H16N4O2S2)], have been synthesized via facile nucleophilic addition reactions of 2.3 equivalents of ferrocenoyl isothiocyanate with o-, m- and p-phenylenediamine, respectively. The structures of the three new synthesized isomers were fully characterized by 1H NMR, 13C NMR, IR and UV-Vis spectroscopy, elemental analyses and cyclic voltammetry. In addition, the structures of acetone monosolvated compound 1 (1·CH3COCH3), as well as compounds 2 and 3, have been determined by single-crystal X-ray diffraction. A combination of intermolecular N-H...S and C-H...S hydrogen bonds connects the components of compound 1·CH3COCH3 into infinite helix chains. Two pairs of different N-H...S and C-H...S intermolecular hydrogen bonds, as well as N-H...O and C-H...π co-operating interactions, link the molecules of compound 2 into a two-dimensional network. In contrast, compound 3 displays a one-dimensional double-chain array via two intermolecular C-H...S hydrogen bonds. Therefore, the three reported positional isomers present unique individual crystal assemblies.

Constructing a green modifier by using glyoxal-urea resin and chitosan to obtain a modified soy protein adhesive with high bonding strength and excellent water resistance.

The manufacturing of soy-based adhesives with high bonding strength, excellent water resistance, and exceptional environmental performance still faces difficulties. In this work, using glyoxal-urea (GU) resin, chitosan (CS), and soy protein isolate (SPI) as the primary raw materials in order to effectively mitigate the release of free formaldehyde commonly found in traditional wood-based panels. Obtaining an adhesive with high strength, excellent water resistance, and a stable cross-linking structure of GU/CSm/SPI (CSm represents different mass fractions of chitosan solution). The adhesive's structure, properties, and bonding mechanism were comprehensively investigated. The results demonstrated that the modified soy protein adhesive exhibited variations in solid content, viscosity, and contact angle, with viscosity showing the most significant change. Combined with 13C NMR and FTIR analysis findings, it can be inferred that a compact network structure was formed by GU resin, CS, and SPI. When the mass ratio of GU/CS/Distilled water with acetic acid/SPI solution was 50/0.5/9.5/130 (GU/CS5/SPI), the modified soy protein adhesive displayed improved performance and higher storage modulus after curing. The plywood prepared at a hot pressing temperature of 180 °C achieved cold water strength of 2.14 MPa, hot water strength of 1.47 MPa, and boiling water strength of 1.21 MPa respectively; all exceeding the requirements specified in national standard GB/T 9846-2015 for Class II plywood. This high bonding strength and water resistant soy-based adhesive, providing a new approach to the development of environmentally friendly adhesives for commercial use.

Positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes functionalized with ethacrynic acid: Synthesis, characterizaion, and antitumor effect

A new family of ethacrynic acid-functionalized, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes (4a-4e) have been designed, synthesis and fully characterized by 1H and 13C NMR, ESI-MS, elemental analysis, and melting point tests. The molecular structure of 3a, one of the precursor complexes, has been determined by single-crystal X-ray diffraction. The cytotoxicity of the obtained complexes toward human cancer cell lines such as HeLa, MGC803, A549, MDA-MB-231, and MCF-7 cells have been investigated by MTT assay. Whereas complexes 4d and 4e showed significantly higher cytotoxicity than cisplatin (the positive control group) and complexes 3a-3e. Moreover, complexes 4d and 4e exhibited a certain selectivity (selectivity index: 7.33 and 7.57) toward MCF-7 cells over MCF-10a normal cells. Glutathione S-transferases (GSTs) activity assay indicate that complexes 4d and 4e exhibited higher GST inhibitory activity than ethacrynic acid (EA, the best characterized GST inhibitor), consistent with their higher cytotoxicity. Further mechanistic studies showed that 4e-induced cell apoptosis may be aroused by the production of ROS, the loss of mitochondrial membrane potential and G2/M phase cell arrest in MCF-7 cells. In addition, the in vivo antitumor effect study on the xenograft mouse models of MCF-7 cells reveal that complex 4e significantly inhibited tumor growth with a higher inhibition efficiency of 68.80 %, in comparison with the groups treated with cisplatin (59.25 %). These results highlight the strong possibility to develop positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes funcionalized with GST inhibitor as promising anticancer agents.

Dihydrofolate reductase inhibitory potential of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as new anticancer derivatives: In-vitro and in-silico studies.

In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety. The resulting compounds have been screened for their dihydrofolate reductase (DHFR) inhibition activity. All the newly synthesized compounds were characterized by 1H NMR, 13C NMR, 19F NMR (spectroscopy when applicable), and HR-ESI-MS spectroscopy techniques. The X-ray crystallography studies have unambiguously confirmed the structure of compounds 6, 11 and 13. Furthermore, their DHFR-inhibitory activity was evaluated in-vitro. The results obtained from the DHFR-inhibitory assay revealed that all the synthesized 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives were highly potent inhibitors, with IC50 values in the range 3.48±0.16-30.37±1.20μM. Ten compounds (15c-15f, 16c-16f, 17e and 17f) among the 32 synthesized 1H-indole-based-meldrum linked 1H-1,2,3-triazole compounds were found to exhibit exceptional inhibitory while the rest of the derivatives showed moderate activities. Additionally, molecular docking analysis of the most active (16f), moderate (15c) and least active (16a) inhibitors reflect excellent binding of 16f with the binding residues of DHFR with higher docking score (-9.13kcal/mol) than that of 15c and 16a. The docking analysis correlates well with the inhibitory potential of these synthesized molecules. Overall, this study may pave the way to medicinal analogues of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as potent DHFR inhibition activity.

Deep eutectic solvent-assisted starch acetylation within stale bread particles to improve water resistance.

Building up from our previous findings on deep eutectic solvents (DES) as reaction promoters for the acetylation of pure wheat starch, the current work explored combinations of reaction time, temperature and acetic anhydride: bread molar ratios to acetylate macromolecules within bread particles relying solely on macromolecule solvation and the slightly basic environment provided by the eutectic mixture. High degree of substitution with acyl groups (DSacyl, 0.73-1.09 as quantified by 1H NMR and confirmed by 13C NMR, and FTIR) was achieved within a short timeframe of 36 min and < 16 acetic anhydride: bread molar ratio. Spectroscopy discarded a major presence of side-reaction products starch carbamates and acetyl urea in reacted samples. Nevertheless, DES acetylation resulted in reacted samples with starch weight average molecular weight (Mw) ranging from 2.62 × 106 to 1.39 × 106 g/mol for the most degraded sample and the partial wash-off of starch and cell wall polysaccharides, which resulted in increased gluten content. Notably, TGA (coupled to real-time FTIR analysis of the evolved gases) suggested a potential enhancement in hydrophobicity and glass transition temperature (Tg) in the reacted samples, with a positive correlation between DSacyl and Tg. These findings emphasize the potential of DES as reaction promoters in complex starchy matrices for esterification reactions.

Discovery of Hydrazine Clubbed Thiazoles as Potential Antidiabetic Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies.

In this study, hydrazine clubbed thiazole derivatives (3a-3j) were obtained by Hantzsch thiazole synthesis and characterized by MS, 1H NMR, and 13C NMR. The inhibitory potentials of the derivatives against diabetes-related enzymes such as aldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) were experimentally determined, and the results were supported by molecular docking. The results showed that the derivatives (3a-3j) displayed varied degree of potential inhibitory activity, with KI values covering the following ranges: 5.47 ± 0.53 to 23.89 ± 1.46 nM for AR and 1.76 ± 0.01 to 24.81 ± 0.15 μM for α-GLY, and with IC50 values 4.94-28.17 μM for α-AMY, as compared to standard epalrestat and acarbose (KI: 34.53 ± 2.52 nM for AR and 23.53 ± 2.72 μM for α-GLY, respectively). The selective activity of these derivatives on antidiabetic enzymes may be important for the treatment of diabetes and may lead to the development of alternative new compounds for this purpose.

Investigation of the InVitro Antioxidant, Anticholinesterase, Antiurease, Antityrosinase, and Cytotoxic Properties of a Novel Compound: 4-Methoxy-2-(4-Methoxyphenyl)Benzo[d][1,3,2]Dioxaborole.

In this study, the structure of a new boron compound obtained using 3-methoxy catechol and 4-methoxy phenyl boronic acid was characterized by 1H, 13C NMR, LC-MS-IT-TOF, UV-Vis and FTIR spectroscopy. The antioxidant activities of the newly synthesized compound were evaluated by DPPH free radical scavenging, ABTS quation radical scavenging and CUPRAC copper reducing capacity methods. Anticholinesterase activities were determined by acetylcholinesterase and butyrylcholinesterase enzyme inhibitor assays. Antiurease and antithyrosinase enzyme inhibition activities were also examined. Cytotoxic effects were evaluated on healthy cell lines and breast and colon cancer cell lines using MTT method. The results showed that the synthesized compound has high antioxidant activity. Especially the average antioxidant activity values obtained at 10 μg/mL concentration were found to be statistically significantly (p < 0.05) higher than the reference values of α-TOC and BHT. When the antioxidant activity data (IC50) were compared separately with α-TOC and BHT reference values, the new compound was found to be more effective. In acetylcholinesterase enzyme inhibition, the average activity values were found to be statistically significantly (p < 0.05) higher than the galantamine reference value. However, no statistically significant difference was observed at BChE (% inhibition) level with galantamine reference value. In terms of urease and tyrosinase enzyme inhibition activities, the urease activity of the synthesized compound was statistically significantly (p < 0.05) lower than the thiurea reference value. Tyrosinase activity was statistically significantly (p < 0.05) lower than kojic acid reference values. The synthesized and characterized compound was found to have no toxic effect on healthy cell lines and did not show any cytotoxic effect on breast cancer (MCF-7) and colon cancer (HT-29) cell lines.

Discovery of Novel Pyrimidine Based Small Molecule Inhibitors as VEGFR-2 Inhibitors: Design, Synthesis, and Anti-cancer Studies.

Receptor tyrosine kinases (RTKs) are potent oncoproteins in cancer that, when mutated or overexpressed, can cause uncontrolled growth of cells, angiogenesis, and metastasis, making them significant targets for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2), is a tyrosine kinase receptor that is produced in endothelial cells and is the most crucial regulator of angiogenic factors involved in tumor angiogenesis. So, a series of new substituted N-(4-((2-aminopyrimidin-5-yl)oxy)phenyl)-N-phenyl cyclopropane- 1,1-dicarboxamide derivatives as VEGFR-2 inhibitors have been designed and synthesized. Utilizing H-NMR, C13-NMR, and mass spectroscopy, the proposed derivatives were produced and assessed. HT-29 and COLO-205 cell lines were used for the cytotoxicity tests. The effective compound was investigated further for the Vegfr-2 kinase inhibition assay, cell cycle arrest, and apoptosis. A molecular docking examination was also carried out with the Maestro-12.5v of Schrodinger. In comparison to the reference drug Cabozantinib (IC50 = 9.10 and 10.66 μM), compound SP2 revealed promising cytotoxic activity (IC50 = 4.07 and 4.98 μM) against HT-29 and COLO-205, respectively. The synthesized compound SP2 showed VEGFR-2 kinase inhibition activity with (IC50 = 6.82 μM) against the reference drug, Cabozantinib (IC50 = 0.045 μM). Moreover, compound SP2 strongly induced apoptosis by arresting the cell cycle in the G1 phase. The new compounds' potent VEGFR-2 inhibitory effect was noted with key amino acids Asp1044, and Glu883, and the hydrophobic interaction was also observed in the pocket of the VEGFR-2 active site by using a docking study. The results demonstrate that at the cellular and enzyme levels, the synthetic compounds SP2 are similarly effective as cabozantinib. The cell cycle and apoptosis data demonstrate the effectiveness of the suggested compounds. Based on the findings of docking studies, cytotoxic effects, in vitro VEGFR-2 inhibition, apoptosis, and cell cycle arrest, this research has given us identical or more effective VEGFR-2 inhibitors.

DNL-17: A Small-Pore Aluminophosphate in ABC-6 Family with 24 Stacking Layers Unraveled by Three-Dimensional Electron Diffraction.

Small-pore aluminophosphate (AlPO) molecular sieves (MSs), particularly those in the ABC-6 family, have gained significant attention for their unique capabilities in selective adsorption and energy storage. However, developing new synthesis strategies for designing AlPOs with three-dimensional (3D) channel systems and determining the structures of nanosized novel AlPO MSs remain challenging tasks. In this study, we introduce a new small-pore AlPO with a 3D channel system, named DNL-17, synthesized by using a diquaternary ammonium compound as an organic structure-directing agent (OSDA). Its crystallographic structure was determined through advanced 3D electron diffraction (ED) techniques and further confirmed by emerging integrated differential phase contrast imaging. DNL-17 exhibits a remarkable 24-layer stacking sequence along the c-axis and features a variety of composite building units (CBUs), including d6r, can, cha, and eri. Significantly, a combination of 3D ED, theoretical calculations, and solid-state 13C NMR reveals that the employed OSDA adopts distinct conformations to stabilize different cages. This finding highlights a novel strategy for constructing AlPO MSs with diverse cage-based CBUs. Furthermore, DNL-17 demonstrates unique selective adsorption properties, particularly in the separation of n-butane and isobutane.