Good Activity Research Articles

MOLECULAR DOCKING DYNAMICS OF SELECTED BENZYLIDENE AMINO PHENYL ACETAMIDES AS TMK INHIBITORS USING HIGH THROUGHPUT VIRTUAL SCREENING (HTVS)

Objective: Thymidylate kinase (TMK) plays a crucial role in bacterial DNA synthesis by catalyzing the phosphorylation of deoxythymidine monophosphate (dTMP) to form deoxythymidine diphosphate (dTDP). Consequently, this enzyme emerges as a promising target for developing novel antibacterial drugs. However, no antibiotics were reported for this target, especially active against Staphylococcus aureus thymidylate kinase. Methods: Benzylidene acetamide-based ligands were examined for their potency using the in silico method. These novel ligand structures were built using ChemDraw software. The protein was retrieved from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) website. The molecular docking and binding free energy calculation by prime Molecular Mechanics in Generalized Bond Surface Area (MM-GBSA) was performed for selected ligands. A 100 ns molecular dynamic simulation was also performed to assess the stability of the potential ligand as TMK inhibitors. Results: All ten molecules have shown good glide scores and hydrophobic and hydrogen hydrophobic hydrogen bonding interactions with Arg48, Arg36, and π-π stacking Phe66 in the TMK enzyme (PDB: 4HLC). Among them, N-(2-ethylphenyl)-2-(4-((4-nitrobenzylidene) amino) phenoxy) acetamide molecule had high XP-docking scores of-3.27 kcal/mol based on extra-precision data. Prime Molecular Mechanics in Generalized Bond Surface Area study (MM-GBSA) studies also showed promising binding affinities that are ΔBind (-65.80), ΔLipo (-28.55), and ΔVdW (-55.10). Phe66 amino acid residue maintained continuous connections with the ligand during MD simulation. This ligand showed promising binding affinity with the SaTMK target. Conclusion: The N-(2-ethylphenyl)-2-(4-((4-nitrobenzylidene) amino) phenoxy) acetamide ligand at the position of the benzene ring displayed nitrogen and oxygen group, thus indicating good potential activity as the inhibitor of TMK to treat antibacterial agents.

Popcorn-like bimetallic palladium/platinum exhibiting enhanced peroxidase-like activity for signal enhancement in lateral flow immunoassay

BackgroundThe lateral flow immunoassay (LFIA) is widely employed as a point-of-care testing (POCT) technique. However, its limited sensitivity hinders its application in detecting biomarkers with low abundance. Recently, the utilization of nanozymes has been implemented to enhance the sensitivity of LFIA by catalyzing the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). The catalytic performance of nanozymes plays a crucial role in influencing the sensitivity of LFIA. ResultsThe Cornus officinalis Sieb. et Zucc-Pd@Pt (CO–Pd@Pt) nanozyme with good peroxidase-like activity was synthesized herein through a facile one-pot method employing Cornus officinalis Sieb. et Zucc extract as a reducing agent. The morphology and composition of the CO–Pd@Pt nanozyme were characterized using TEM, SEM, XRD, and XPS. As a proof of concept, the as-synthesized CO–Pd@Pt nanozyme was utilized in LFIA (CO–Pd@Pt-LFIA) for the detection of human chorionic gonadotropin (hCG). Compared to conventional gold nanoparticles-based LFIA (AuNPs-LFIA), CO–Pd@Pt-LFIA demonstrated a significant enhancement in the limit of detection (LOD, 0.08 mIU/mL), which is approximately 160 times lower than that of AuNPs-LFIA. Furthermore, experiments evaluating accuracy, precision, selectivity, interference, and stability have confirmed the practical applicability of CO–Pd@Pt-LFIA for hCG content determination. SignificanceThe present study presents a novel approach for the synthesis of bimetallic nanozymes through environmentally friendly methods, utilizing plant extracts as both protective and reducing agents. Additionally, an easily implementable technique is proposed to enhance signal detection in lateral flow immunoassays.

Design, Synthesis, and Biological Activity of Novel Triketone-Containing Phenoxy Nicotinyl Inhibitors of HPPD.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 μM, demonstrating superior activity compared with mesotrione (0.28 μM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.

Crystal structure and in vitro biological studies of a Pt(II) complex based on gallic acid and triphenylphosphine

Gallic acid is a natural polyphenol found in a variety of fruits, plants and nuts that has several biological properties, such as anti-oxidant, anti-inflammatory, and antitumor, among other activities. Some studies have proven that metal complexation could be an interesting strategy to enhance its pharmacological activities. Taking that into account, we report here the synthesis, spectral characterization (FTIR, 1H, 13C{1H}, 31P{1H} and 195Pt{1H} NMR), structural analysis, and biological activities of a new platinum(II) complex bearing gallic acid (ga) and triphenylphosphine (PPh3) as ligands. Spectral data suggest that a gallic acid molecule chelates the metal via two deprotonated phenolic oxygen atoms and two monodentate triphenylphosphines complete the coordination sphere. Furthermore, X-ray data support that the platinum(II) ion adopts a slightly distorted square-planar coordination environment. Time-dependent 1H NMR spectra at room temperature suggest that the complex is very stable in DMSO for at least 48 h. Subsequently, the cytotoxic activity of the platinum(II) complex was assessed against chronic myelogenous leukemia cells (k562) and in a non-cancerous cell line (LLCMK2). The complex was more active than gallic acid, cisplatin and carboplatin against the K562 cell line, exhibiting outstanding activity (IC50 = 0.75 μM). When tested against Mycobacterium tuberculosis, the complex showed good activity with a MIC value of 3.75 μg/mL. The results reported here reinforce the antitumor and antimycobacterial potential of metal complexes containing gallic acid and derivatives.

Chemical constituents from uncaria laevigata and their vasodilatory activities in vitro and action mechanism

A new triterpenoid compound 1* (scandine A1) was obtained from 95% ethanol extract of Uncaria laevigata. Meanwhile, eleven described compounds were also isolated for the first time from Uncaria laevigata. Herein, compound 2 exhibited strong diastolic cardio-cerebrovascular activity (EC50BA = 9.22 μM and EC50CA = 14.65 μM), which was not been previously described. Compound 1* also showed certain diastolic cardio-cerebrovasculary activity. Network pharmacology indicated that the diastolic cardio-cerebrovascular activity of compound 2 was most correlated with the Ras signalling pathway. Molecular docking confirmed that it exhibited strong binding activity with target protein (matrix metalloproteinase inhibitor-1). Moreover, compound 2 demonstrated significant potential on cardio-cerebrovascular activity in vitro. Overall, compounds 1* and 2 with good diastolic cardio-cerebrovascular activity were discovered in this work.

In situ surface etching strategy for bimetallic MOFs-derived oxides and their catalytic properties

MOFs and their derivatives are excellent carriers with large specific surface area. Here, we propose a new strategy to engineer a supported-Pt core shell MOF-derived metal oxide catalyst. In this work, ZnCo-glycol microspheres were used as sacrificial templates, and the pre-prepared Pt nanoparticles were modified in MOFs during the in situ surface etching strategy. Compared to the ZnCo-2MI-330 and ZnCo–Pt-330, ZnCo–Pt-2MI-330 presents good catalytic activity (T10 = 110 °C,T90 = 123 °C) and excellent stability on CO oxidation reaction. By detailed characterization, ZnCo–Pt-2MI-330 remains the original pore structure of MOFs and provides a larger specific surface area, while the addition of Pt NPs changes the content of active species (the high ratio of Co3+ and active oxygen species) in the metal oxides. More importantly, the strategy effectively improves the noble metal catalysts are apt to lose their activities during the thermal catalytic caused by the serious working environment.

Glutathione‑iron hybrid nanozyme-based colorimetric sensor for specific and stable detection of thiram pesticide on fruit juices

Given the potential dangers of thiram to food safety, constructing a facile sensor is significantly critical. Herein, we presented a colorimetric sensor based on glutathione‑iron hybrid (GSH-Fe) nanozyme for specific and stable detection of thiram. The GSH-Fe nanozyme exhibits good peroxidase-mimicking activity with comparable Michaelis constant (Km = 0.551 mM) to the natural enzyme. Thiram pesticides can specifically limit the catalytic activity of GSH-Fe nanozyme via surface passivation, causing the change of colorimetric signal. It is worth mentioning that the platform was used to prepare a portable hydrogel kit for rapid qualitative monitoring of thiram. Coupling with an image-processing algorithm, the colorimetric image of the hydrogel reactor is converted into the data information for accurate quantification of thiram with a detection limit of 0.3 μg mL−1. The sensing system has good selectivity and high stability, with recovery rates in fruit juice samples ranging from 92.4% to 106.9%.

Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 ∼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 ∼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

Exploring self-crosslinked hydrogel: Carboxymethyl chitosan and oxidized alginate for wound healing applications

This study reports the development and evaluation of self-healing hydrogel composed of carboxymethyl chitosan (CmCh) and oxidized alginate, with a focus on wound healing applications. Oxidized alginate was synthesized via metaperiodate oxidation and characterised. The hydrogels were formulated using Schiff base reactions with two weight ratios of oxidized alginate and CmCh, and their cross-linking mechanism was proposed. The developed hydrogels were characterised for their gelation, pH, self-healing capability, conductivity, and injectability. The optimized hydrogel was further evaluated for antibacterial activity, cytotoxicity, haemocompatibility, and in vitro wound healing studies. Results revealed that hydrogels with the lowest ratio of oxidized alginate to CmCh exhibited superior gelation, tensile strength, and injectability without needle clogging. Additionally, rapid self-healing of hydrogels was confirmed via Scanning Electron Microscope (SEM) analysis. The optimized hydrogel displayed good antibacterial activity against Staphylococcus aureus and Escherichia coli, alongside haemocompatibility. Additionally, in vivo studies demonstrated comparable wound healing efficacy to marketed formulations and significant improvement over control groups. These findings indicates the potential of self-healing hydrogels made up of oxidized alginate and CmCh for tissue engineering applications.

Different M-doped Ni3S2/FeS (M=Co, Cr, Cu, Zn) hybrid nanosheet arrays for overall urea splitting and seawater oxidation reaction

Hydrogen production by electrolysis of water is gradually becoming the main way to obtain green energy, but due to the scarcity of fresh water resources in the world, so the study of urea and seawater electrolysis has become an important work. In this experiment, different metal ions M (M=Co, Cr, Cu, Zn) doped Ni3S2/FeS were investigated as catalysts with good catalytic activity in hydrogen evolution reaction (HER) as well as in urea oxidation reaction (UOR) in urea electrolyte, and Co-Ni3S2/FeS and Cr-Ni3S2/FeS, which performed well in HER and UOR, were assembled into an electrolytic cell for the overall urea decomposition (1.50 V @ 10 mA cm−2). Density Functional Theory (DFT) calculations demonstrated that Co-Ni3S2 possesses a lower free energy for H, while FeS possesses a higher density of states (DOS) near the Fermi energy level, and such a composite structure promotes significantly the catalytic activity of HER. The catalytic effect of oxygen evolution reaction (OER) was further investigated in the seawater electrolyte, and the results showed that the performance of Co-Ni3S2/FeS catalyst was better, and certain ions in seawater affected durability of the catalyst. The electronic structure of the catalyst was investigated through the characterization of the catalyst and combined with the special morphology jointly promote the catalytic reaction in electrolysis experiments, which provides a candidate catalyst for electrolysis of urea and seawater oxidation reaction.

Catalytic promiscuity, cytotoxicity and protein cleavage mediated by mononuclear copper(II) complexes: oxidative and hydrolytic activities

In this work, we describe the synthesis and structural and spectroscopic characterizations of two copper(II) complexes, [(Cu)(L1)(Cl2)].4H2O (1), where L1 is 2-(pyridin-2-yl)-1,3-bis(pyridin-2-ylmethyl)-hexahydropyrimidine, and [Cu(L2)](ClO4)2 (2), where L2 is N1,N1,N3-tris(pyridin-2-ylmethyl)propane-1,3-diamine. The crystalline structure analysis indicates that both complexes are mononuclear and pentacoordinated compounds. In the case of complex 1, it bears a neutral charge, with the ligand coordinating to the Cu(II) center in a tridentate manner, utilizing N-donor atoms. Additionally, two cis-chlorido ligands completing the coordination sphere. On the other hand, complex 2 is a cationic complex, with the ligand coordinated in a pentadentate manner, with only N-donor atoms for coordination around the Cu(II). Complex 1 showed catalytic promiscuity, displaying hydrolytic and oxidative activity. The hydrolytic activity was investigated using bis(2,4-dinitrophenyl) phosphate (2,4-BDNPP) as a phosphodiester substrate and applying the Michaelis–Menten approach, obtaining the following kinetic parameters: kcat = 1.21 × 10-4 s−1; KM = 3.35 × 10-3 molL-1. Complex 1 also accelerates the oxidation of the 3,5-di-tert-butylcatechol (3,5-DTBC) substrate with catalytic efficiency equal to 6.11 L mol-1s-1. Interestingly, we demonstrated that this Cu(II) complex 1 can also cleave the very stable peptide bonds from BSA (bovine serum albumin) through an oxidative mechanism using ascorbate as a reducing agent. Complexes 1 and 2 show good cytotoxic activity against two cancer cell lines: A431 from human squamous cell carcinoma and K562 from chronic myeloid leukemia. This study showed that complexes 1 and 2 are selective towards cancer cells.

Design, synthesis and biological evaluation of new RNF126-based p300/CBP degraders

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin–proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC50) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin–proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.

Nickel-hydroxide decorated trimanganese-tetroxide nanorods supported on graphene as bifunctional electrocatalyst for metal–air batteries

Manganese oxide, such as Mn3O4, is one of promising material as electrocatalyst in air–cathode for metal–air battery due to low cost, high catalytic activity and good stability. Although pure Mn3O4 material exhibits excellent catalytic activity to ORR, it is severely limited by its intrinsically low conductivity and high over-potential toward OER. In this work, the hybrid materials of nickel-hydroxide-decorated nanorods of trimanganese-tetroxide supported on reduced-graphene have been prepared by one-step hydrothermal method. The composite materials are used as bifunctional cathode catalysts to ORR/OER, and investigated by the technologies of rotating disk electrode and metal–air batteries. The results indicate that the hybrid material of Mn-Ni/rGO use as catalyst in air–cathode for Al/Zn–air battery has good catalytic activity. Based on analysis of scanning electron microscope and X-ray photoelectron spectroscopy, the composite material shows good performance owing to the improvement of conductivity supported on graphene, more Mn4+ on the surface of hybrid material, the coexistence of Mn3+/Mn4+ redox couple, and the synergism between nickel-hydroxide and graphene.

Porous hollow nanospheres nickel phosphide and its high catalytic hydrogenation performance on naomaohu coal soluble portion and model compounds

The catalytic conversion of oxygen-containing aromatic ring in lignite under mild conditions is crucial to obtain clean liquid fuel. Here, hollow nanosphere Ni3P-500–24 catalysts were prepared at a calcination temperature of 500 °C and acid-etching time of 24 h. The porous hollow nanospheres structure could expose more catalytic sites, and the electron-rich nickel exhibited a good catalytic activity. The conversion rate of benzyl phenyl ether (BPE) was 100 % (140 ℃, 1 MPa H2, 2 h), and the main products were methylcyclohexane and cyclohexanol, indicating that the catalyst had good catalytic hydrocracking performance. In addition, the catalyst exhibited certain deoxygenation activity and high product selectivity for other oxygen-containing model compounds. For the catalytic hydrogenation of Naomaohu coal (NMHC) soluble portion, the content of alkanes increased from 19 % to 47 %, while the content of oxygen-containing compounds decreased from 56 % to 21 %, which further demonstrate that the catalyst have good catalytic hydrogenation and deoxygenation performance. Density Functional Theory (DFT) calculations showed that the properties of the Ni3P-500–24 catalyst was similar to noble metal, which could activate H2 to produce two kind of active hydrogen: H radical and diatomic hydrogen. The synergistic pathways for the transfer of active hydrogen during the catalytic hydroconversion (CHC) process were analyzed. Above results could provide theoretical guidance for the conversion of lignite into high-quality clean liquid fuels.

Design, Synthesis, and Biological Evaluation of Pyridazinone-Containing Derivatives As Novel Protoporphyrinogen IX Oxidase Inhibitor.

Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound 10ae, known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO (NtPPO) with an inhibition constant (Ki) value of 0.0338 μM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with NtPPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate (10bh), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (Leaf mustard, Chickweed, Chenopodium serotinum, Alopecurus aequalis, Poa annua, and Polypogon fugax) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound (10bh) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.

Silica-assisted Pt1/CeO2 single-atom catalyst for enhancing the catalytic combustion performance of VOCs by inducing H2O activation

Due to the competitive adsorption of water and reactants at the active sites, especially the water toxicity of platinum-based single-atom catalysts, it is of great importance to improve the low-temperature activity and the water resistance of catalysts for the catalytic combustion of benzene. In this work, it was found that constructing a SiO2 shell layer on the catalyst not only "immobilized" the Pt single atoms, but also effectively weakened the adsorption of H2O on the Pt active sites, which resulted in excellent water resistance of the Pt single-atom catalysts. The comprehensive characterization results demonstrated that the participation of water molecules in the catalytic oxidation reaction of benzene could be effectively promoted by enhancing the strong metal-support interactions (SMSI) at the core-shell interface, which would change the electronic structure of the catalyst surface. As a result, the Pt1/CeO2@SiO2-4 catalyst with a Pt-O-Si active interface exhibits good activity (T = 190 °C) as well as excellent water resistance under the wet condition (10 vol%). This project provides a promising strategy for the design of Pt-based core-shell catalysts with excellent water resistance.

Comparative evaluation of antimicrobial activity of spinel structured transition metal ferrites supported on reduced graphene oxide against pathogenic strains of bacteria and fungi.

One of the global challenges for living things is to provide pollution and harmful microbes-free environment. In this study, magnetically retrievable spinel-structured manganese zinc ferrite (Mn0.5Zn0.5Fe2O4) (MZF) was synthesized by a facile solvothermal method. Further, the MZF with different weight percentages (10wt%, 50wt%, and 80wt%) were supported on reduced graphene oxide (rGO). The phase purity and morphology of MZF and MZF/rGO nanocomposite were confirmed by X-ray diffraction technique and scanning electron microscopy, respectively. The Fourier transform infrared spectroscopy, Raman, UV-visible spectroscopy, and thermogravimetric analyses of the as-synthesized nanocomposites were examined for the detection of various chemical groups, band gap, and thermal properties, respectively. The MZF/rGO nanocomposite exhibited significant antibacterial and antifungal activity against Eggerthella lenta, Enterococcus faecalis, Klebsiella pneumonia, Pseudomonas aeruginosa, and Candida albicans compared to bare MZF and rGO. The high surface area of rGO plays a crucible role in antimicrobial analysis. Additionally, the anti-bacterial and fungal activity is compared by synthesizing various metal ferrites such as MnFe2O4, ZnFe2O4, and Fe3O4. The 50wt% MZF/rGO nanocomposite exhibits significantly high antibacterial activity. However, 10wt% MZF/rGO nanocomposite shows good antifungal activity than Fe3O4, MnFe2O4, ZnFe2O4, MnZnFe2O4, 50wt%, and 80wt% MZF/rGO nanocomposites. These findings suggest that the prepared ferrite nanocomposites hold promise for microbial inhibition.

Cu-BTC Derived Mesoporous CuS Nanomaterial as Nanozyme for Colorimetric Detection of Glutathione.

In this paper, Cu-BTC derived mesoporous CuS nanomaterial (m-CuS) was synthesized via a two-step process involving carbonization and sulfidation of Cu-BTC for colorimetric glutathione detection. The Cu-BTC was constructed by 1,3,5-benzenetri-carboxylic acid (H3BTC) and Cu2+ ions. The obtained m-CuS showed a large specific surface area (55.751 m2/g), pore volume (0.153 cm3/g), and pore diameter (15.380 nm). In addition, the synthesized m-CuS exhibited high peroxidase-like activity and could catalyze oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue product. Peroxidase-like activity mechanism studies using terephthalic acid as a fluorescent probe proved that m-CuS assists H2O2 decomposition to reactive oxygen species, which are responsible for TMB oxidation. However, the catalytic activity of m-CuS for the oxidation of TMB by H2O2 could be potently inhibited in the presence of glutathione. Based on this phenomenon, the colorimetric detection of glutathione was demonstrated with good selectivity and high sensitivity. The linear range was 1-20 μM and 20-300 μM with a detection limit of 0.1 μM. The m-CuS showing good stability and robust peroxidase catalytic activity was applied for the detection of glutathione in human urine samples.

Synthesis, design, and antiproliferative evaluation of 6-(N-Substituted-methyl)pyrazolo[3,4-d]pyrimidines as the potent anti-leukemia agents

Pyrazolopyrimidine derivatives, including pyrazolopyrimidines, 6-aminopyrazolopyrimidines, 6-[(formyloxy)methyl]pyrazolopyrimidines, 6-(hydroxymethyl)pyrazolopyrimidine, and 6-(aminomethyl)pyrazolopyrimidines have been successfully prepared and tested against NCI-H226, NPC-TW01, and Jurkat cancer cell lines. Among the tested pyrazolopyrimidine compounds, we found 6-aminopyrazolopyrimidines and 6-(aminomethyl)pyrazolopyrimidines with essential o-ClPh or p-ClPh substituted moieties on N-1 pyrazole ring exhibited the best IC50 inhibition activity for Jurkat cells. Furthermore, optimization of the SAR study on the C-6 position of pyrazolopyrimidine ring demonstrated that 6-(N-substituted-methyl)pyrazolopyrimidines 17b, 17d, and 19d possessed the significant IC50 inhibitory activity for the different leukemia cell lines, especially for Jurkat, K-562, and HL-60. On the other hand, further SAR inhibition and docking model studies revealed that compound 19d, which has a 3-(1H-imidazol-1-yl)propan-1-amino side-chain on the C-6 position, was able to form four hydrogen bonds with residues Ala226, Leu152, and Glu194 and specifically extended into the P1 pocket subsite with Aurora A, resulting in improved inhibitory activity almost similar to SNS-314. To explore the anti-cancer mechanism, compound 19d was measured by Western blot analysis in Jurkat T-cells, however, it showed non-responsibility to Aurora B. For the further structural modifications on the lateral chain of compound 19d, compounds 24 with longer lateral chain were designed and synthesized for testing leukemia cell lines. However, compounds 24 was significantly decrease inhibition potency against leukemia cell lines. Based on the in-vitro results, compounds 17b and 19d could be considered to be the best potential lead drug in our study for the development of new and effective therapies for leukemia treatment. On the other hand, the DHFR inhibition results indicated compound 19d possessed good inhibitory activity and better than the reported naphthalene derivative. Through further comparisons of the model superposition of three-dimensional (3D) conformations in DHFR, compound 19d presented a similar structural alignment to Methotrexate and the reported naphthalene derivative and led to similar drug-like functional relationships. As a results, compound 19d would be a potential DHFR inhibitor for anti-leukemia drug candidate.

A novel Pt2+ complex containing 1,4-benzodioxan-6-amine: Stability, DNA binding, and antitumor effects against human breast cancer cells

In this work, a new platinum(II) complex was prepared by the reaction of K2PtCl4 with 1,4-benzodioxan-6-amine (bda) at room temperature in the molar ratio 2:1 (L:M). The complex was characterized by physicochemical (elemental analysis, TGA/DTA, and conductivity measurements) and spectroscopic methods (UV–Vis, FTIR, 1H, 13C and 195Pt NMR). According to the spectroscopic data, two bda ligands coordinate to the platinum ion in a monodentate manner through the nitrogen atom to give the complex cis-[PtCl2(bda)2]. Stability studies were carried out under different conditions and showed that the complex is stable in pure DMF, although it undergoes slow solvolysis in DMSO. The interaction of this complex with calf thymus DNA (CT-DNA) was studied using circular dichroism (CD), electronic absorption and fluorescence spectroscopy. The complex binds to CT-DNA with a Kb value of 1.06 ​× ​103 ​M−1 and according to data from CD and fluorescence spectroscopy, appears to interact with DNA by electrostatic forces and or other no intercalative binding mode. Compared to cisplatin, the complex exhibited good cytotoxic activity and selectivity against the MCF-7 tumor cell line, displaying an IC50 value of 17.33 ​± ​1.1 ​μM, as well as inhibited MCF-7 ​cells migration.