2B Compounds Research Articles

Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth.

Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β-19α-trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT-qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M-TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells.

Evaluation of Cytotoxic, COX Inhibitory, and Antimicrobial Activities of Novel Isoxazole-carboxamide Derivatives

Abstract: Isoxazole derivatives are one of the heterocyclic structures that have various biological activities. Objective: This study aimed to design and synthesize novel isoxazole derivatives and evaluate their cytotoxic, cyclooxygenase (COX) inhibitory, and antimicrobial activities. Methods: Coupling reactions of aniline derivatives and isoxazole carboxylic acid have been established to synthesize chloro-fluorophenyl-isoxazole carboxamide derivatives. The synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and evaluated by MTS, COX kit, and antimicrobial microdilution assays. Results: The synthesized compounds showed moderate to potent cytotoxic activity against all the screened cancer cell lines (except 2b against HepG2) with an IC50 range of 0.107-77.83 μg/ml. The results showed that the most potent compound against cervical cancer cell line (HeLa) was the 2b compound, with an IC50 value of 0.11±0.10 μg/ml, which is less than the IC50 for the potent anticancer drug Doxorubicin. While the 2a and 2b compounds have potential antiproliferative activities against Hep3B with IC50 doses of 2.774±0.53 and 3.621±1.56 μg/ml, respectively. Furthermore, 2c compound was the most active against MCF7, with an IC50 value of 1.59±1.60 μg/ml. In addition, the most potent isoxazole derivative against the COX1 enzyme was the 2b compound, with an IC50 value of 0.391 μg/ml, and compound 2a had a good selectivity ratio of 1.44 compared to the Ketoprofen positive control. However, compound 2c showed antifungal activity against Candida albicans with an MIC value of 2.0 mg/ml in comparison to the antifungal drug Fluconazole (MIC = 1.65 mg/ml). Conclusion: The synthesized compounds could be candidates for anticancer drugs in the future, and other analogues and cytotoxicity evaluations should be conducted.

Investigation of cytotoxic properties of some isoindole-related compounds bearing silyl and azide groups with in vitro and in silico studies

This study aims to evaluate the synthesis of isoindole-1,3-dione analogues and their cytotoxic potential. A549 and HeLa cells exposed to 250–100–50–25 µM doses of each derivative were incubated for 24, 48, and 72 h. The cytotoxicity of the isoindole-1,3-dione derivatives was analyzed using the cell growth inhibition assay and the cell membrane damage test. (3aR,5R,6R,7aS)-5-Azido-2-benzyl-6-hydroxyhexahydro-1H-isoindole-1,3(2H)-dione (1d), (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-ethylhexahydro-1H-isoindole-1,3(2H)-dione (2a), and (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (2b) compounds inhibited the growth of the A549 and HeLa cells caused membrane damage and exhibited a dose-dependent cytotoxic effect on lung and cervical carcinoma cells. The effect of tert-butyldiphenylsilyl (TBDPS) groups on cytotoxicity was observed in compounds 2a and 2b, but not in the other compounds. Considering the effect of groups attached to the nitrogen atom, the best activity was exhibited in 2b molecule to which the methyl group is attached. Additionally, the interactions of compounds (3aR,5R,6R,7aS)-5-azido-6-hydroxy-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (1b), 1d, 2a and 2b with mammalian rapamycin target, human ribosomal S6 kinase 1 and human epidermal growth factor receptor were investigated by molecular docking studies, . According to the docking results, 2a and 2b compounds containing a TBDPS group have stronger binding energies than 1b and 1d compounds against all target receptors.

Antioxidant and Anticancer Potential of the New Cu(II) Complexes Bearing Imine-Phenolate Ligands with Pendant Amine N-Donor Groups

Cu(II) complexes bearing NNO-donor Schiff base ligands (2a, b) have been synthesized and characterized. The single crystal X-ray analysis of the 2a complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations. The monomeric nature of 2a and 2b species is maintained in solution. Antioxidant activities of the ligands (1a, b) and Cu(II) complexes (2a, b) were determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH.) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS+). Our results demonstrated that 2a showed better antioxidant activity. MTT assays were performed to assess the toxicity of ligands and Cu(II) complexes in V79 cells. The antiproliferative activity of compounds was tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and SW620 (colorectal carcinoma) and on MRC-5 (normal lung fibroblast). All compounds showed high cytotoxicity in the all-cell lines but showed no selectivity for tumor cell lines. Antiproliferative activity by clonogenic assay 2b showed a more significant inhibitory effect on the MCF-7 cell lines than on MRC-5. DNA damage for the 2b compound at 10 µM concentration was about three times higher in MCF-7 cells than in MRC-5 cells.

A C 54 B 2 Polycyclic π-System with Bilayer Assembly and Multi-Redox Activity

A C ₅₄ B ₂ Polycyclic π-System with Bilayer Assembly and Multi-Redox Activity

Evaluation and optimized selection of supersaturating drug delivery systems of posaconazole (BCS class 2b) in the gastrointestinal simulator (GIS): An in vitro-in silico-in vivo approach

Supersaturating drug delivery systems (SDDS) have been put forward in the recent decades in order to circumvent the issue of low aqueous solubility. Prior to the start of clinical trials, these enabling formulations should be adequately explored in in vitro/in silico studies in order to understand their in vivo performance and to select the most appropriate and effective formulation in terms of oral bioavailability and therapeutic outcome. The purpose of this work was to evaluate the in vivo performance of four different oral formulations of posaconazole (categorized as a biopharmaceutics classification system (BCS) class 2b compound) based on the in vitro concentrations in the gastrointestinal simulator (GIS), coupled with an in silico pharmacokinetic model to predict their systemic profiles. Recently published intraluminal and systemic concentrations of posaconazole for these formulations served as a reference to validate the in vitro and in silico results. Additionally, the morphology of the formed precipitate of posaconazole was visualized and characterized by optical microscopy studies and thermal analysis. This multidisciplinary work demonstrates an in vitro-in silico-in vivo approach that provides a scientific basis for screening SDDS by a user-friendly formulation predictive dissolution (fPD) device in order to rank these formulations towards their in vivo performance.

Effects of Mn substitution on crystal structure, magnetic and magnetocaloric properties of (Co1−xMnx)2B compounds

The crystal structure, magnetic and magnetocaloric properties of (Co1−xMnx)2B (x = 0.0, 0.1, 0.2, 0.25, 0.3, 0.35, 0.40) compounds were investigated by x-ray powder diffraction (XRD) and magnetization measurements. All compounds crystallize in a body-centred tetragonal single phase with the CuAl2-type structure. Due to the changes of lattice stability and ferromagnetic–antiferromagnetic exchange coupling interaction, the room temperature magnetization and the Curie temperature (TC) of (Co1−xMnx)2B compounds first increases at about x = 0.1 and then decreases with the substitution of Mn for Co. Second-order phase transition was confirmed based on the isothermal magnetization curves and the isothermal entropy change (ΔSM) was determined for the samples with x = 0.3, 0.35 and 0.4. The maximal magnetic entropy (|ΔSM|) under a field change from 0 to 5 T are found to be 2.49, 2.37 and 2.02 J kg−1·K for x = 0.3, 0.35 and 0.4, respectively. The corresponding relative cooling powers (RCP) are evaluated to be 59.74, 78.94 and 113.50 J kg−1. Given the low cost of Co, Mn and B, (Co1−xMnx)2B compounds may come as an base compound for a more efficient magnetocaloric material.

Biorelevant Dissolution Models for a Weak Base To Facilitate Formulation Development and Overcome Reduced Bioavailability Caused by Hypochlordyria or Achlorhydria.

In this study, two dissolution models were developed to achieve in vitro-in vivo relationship for immediate release formulations of Compound-A, a poorly soluble weak base with pH-dependent solubility and low bioavailability in hypochlorhydric and achlorhydric patients. The dissolution models were designed to approximate the hypo-/achlorhydric and normal fasted stomach conditions after a glass of water was ingested with the drug. The dissolution data from the two models were predictive of the relative in vivo bioavailability of various formulations under the same gastric condition, hypo-/achlorhydric or normal. Furthermore, the dissolution data were able to estimate the relative performance under hypo-/achlorhydric and normal fasted conditions for the same formulation. Together, these biorelevant dissolution models facilitated formulation development for Compound-A by identifying the right type and amount of key excipient to enhance bioavailability and mitigate the negative effect of hypo-/achlorhydria due to drug-drug interaction with acid-reducing agents. The dissolution models use readily available USP apparatus 2, and their broader utility can be evaluated on other BCS 2B compounds with reduced bioavailability caused by hypo-/achlorhydria.

New antiproliferative 7-(4-(N-substituted carbamoylmethyl)piperazin-1-yl) derivatives of ciprofloxacin induce cell cycle arrest at G2/M phase

New N-4-piperazinyl derivatives of ciprofloxacin 2a–g were prepared and tested for their cytotoxic activity. The primary in vitro one dose anticancer assay experienced promising cytotoxic activity against different cancer cell lines especially non-small cell lung cancer. Independently, compounds 2b, 2d, 2f and 2g showed anticancer activity against human non-small cell lung cancer A549 cells (IC50=14.8, 24.8, 23.6 and 20.7μM, respectively) compared to the parent ciprofloxacin (IC50 >100μM) and doxorubicin as a positive control (IC50=1μM). The flow cytometric analysis for 2b showed dose dependent G2/M arrest in A549 cells. Also, 2b increased the expression of p53 and p21 and decreased the expression of cyclin B1 and Cdc2 proteins in A549 cells without any effect on the same proteins expression in WI-38 cells. Specific inhibition of p53 by pifithrin-α reversed the G2/M phase arrest induced by the 2b compound, suggesting contribution of p53 to increase. Taken together, 2b induced G2/M phase arrest via p53/p21 dependent pathway. The results indicate that 2b can be used as a lead compound for further development of new derivatives against non-small cell lung cancer.

Synthesis of <i>α</i>-Naphthol and 2,4,7-Trimethyl-Quinolin-5-ol by Using Manganese (III) Acetate and Analysis of Its Antimicrobial Properties

This study involves the aromatization reactions of some ketone derivatives through Manganese (III) acetate. The ketone derivatives used in the study are α-tetralone (1a), 2,4,7-trimethyl-7,8-dihydro quinolinone (1b). At the end of the aromatization reactions of these ketone derivatives the synthesized structures of α-naphthol (2a), 2,4,7-trimethylquinoline-5-ol (2b) were identified by spectroscopic methods such as IR, 1H-NMR, 13C-NMR, FAB-MS respectively. Micro-organism types such as Escherichia coli, ATCC 25922, Klepsiella pneumoniae, Staphylococcus aureus NRRL B767, Salmonella typhimurium NRRLB 4420, Bacillus subtilis NRS 744, Bacillus cereus ATCC 11778, Micrococcus luteus ATCC-9341, Listeria monoaytopenus ATCC-7644 bacteria and yeast fungus Candida albicans were used to study the anti-microbial properties of the synthesized 2b compound. The obtained results have determined that compound number 2b has a good antibacterial impact on Bacillus subtilis (NRS-744).

Imidazole, pyrimidine and diazepine containing heteroaryl-substituted heterocyclic salts as efficient ligand precursors for Mizoroki–Heck coupling reaction: synthesis, structural characterization and catalytic activities

The nine new heteroaryl-substituted imidazolidinium (1a–c), pyrimidinium (2a–c) and diazepinium (3a–c) salts as N-heterocyclic carbene (NHC) precursors were synthesized in good yields and entirely characterized using elemental analyses and conventional spectroscopic methods. In situ formed complexes from heterocyclic salts (1–3), Pd(OAc)2 and in the presence of KOBut as a base were tested as catalysts for the Mizoroki–Heck coupling reaction in an aqueous media and very high yields were achieved. 1,3-Di(5-methylthiophen-2-ylmethyl)pyrimidinium hexafluorophosphate salt (2b) was structurally characterized by single-crystal X-ray diffraction. In the 2b compound (C16H21N2S2)+[PF6]−, the terminal thiophene rings are twisted with a dihedral angle of 72.8(3)°. In the pyrimidine ring, the three successive C atoms between the N atoms are disordered over two positions [occupancy ratio 0.753(12):0.247(12)]. In the crystal, neighboring molecules are linked by C–H…F hydrogen bonds, running along the b axis.

Microstructure, Growth Kinetics, and Abrasive Wear Resistance of Boride Layers on Fe–30% Cr Alloy

Two boride layers are found to form at the interface between reacting phases in the course of boriding a Fe–30% Cr alloy in boron powder with KBF4 (activator) in the temperature range of 850–950°C and reaction times 3600–43200 sec (1–12 h). Each of these layers is single-phase structurally (crystallographically) and two-phase compositionally (chemically). The outer boride layer bordering boron consists of the crystals of the (Fe, Cr)B and (Cr, Fe)B compounds, while the inner layer adjacent to the alloy base comprises the crystals of the (Fe, Cr)2B and (Cr, Fe)2B compounds. The characteristic feature of both layers is a profound texture. Diffusional layer-growth kinetics are close to parabolic and can alternatively be described by a system of two non-linear differential equations dx/dt = (kB/x) – (rgkFe/py), dy/dt = (kFe/y) – (qkB/sgx), where x is the outer FeB layer thickness (m), y is the inner Fe2B layer thickness (m), kB is the FeB layer growth-rate constant (m2⋅sec–1), kFe is the Fe2B layer growth-rate constant (m2⋅sec–1), g is the ratio of the FeB and Fe2B molar volumes, p = q = r = 1, and s = 2 (factors from the chemical formulae of FeB and Fe2B). The temperature dependence of the layer growth-rate constants obeys a relation of the Arrhenius type K = Aexp (–E/RT), where K stands for any constant, A is the frequency factor, E is the activation energy, R is the gas constant, and T is the absolute temperature. Application of the least-squares fit method yielded the following equations: kB = 3.42⋅10–8⋅exp(–175.4 kJ × × mol–1/RT) m+⋅sec–1, kFe = 7.45⋅10–9 exp(–144.6 kJ⋅mol–1/RT) m2⋅sec–1. Microhardness values are 18.1 GPa for the outer boride layer, 15.2 GPa for the inner layer, and 1.75 GPa for the alloy base. The dry abrasive wear resistance of the outer boride layer, found from mass loss measurements, is more than 300 times greater than that of the Fe–30% Cr alloy base. Such a huge increase in wear resistance is due to the microstructure of boride layers having a peculiar regular arrangement of enhanced rigidity.

Interaction of 25% chromium steel with boron powder

Thermochemical treatment of industrial chromium steel (15Kh25T–25% Cr) in amorphous boron powder in the temperature range 850–950°C and reaction times up to 43200 sec (12 h) results in the formation of two boride layers at the steel–boron interface. The microstructure of the outer layer bordering the boron phase consists of elongated crystals of the (Fe,Cr)B and (Cr,Fe)B compounds, while that of the inner layer adjacent to the steel base consists of elongated crystals of the (Fe,Cr)2B and (Cr,Fe)2B compounds. Both layers reveal a pronounced texture. Their diffusional growth kinetics is close to parabolic x 2 = 2k 1 t, where x is the total thickness of both layers (m), k 1 is the layer growth-rate constant (m2 ∙ sec–1), and t is time (sec). The temperature dependence of the growth-rate constant of boride layers on the steel surface is described by a relation of the Arrhenius type k 1 = 1.72 ∙ 10–8 exp (–137.1 kJ · mole–1/RT). Microhardness values are 17.8 GPa for the outer layer, 15.9 GPa for the inner layer, and 1.70 GPa for the steel base. The dry abrasive wear resistance of borided steel samples is more than 250 times greater than that of non-borided ones.

Phase composition and morphology as a function of depth for boride coatings grown on Fe-Ni alloys

Two Fe-Ni alloys very differing in Ni content, Fe64Ni36 and Fe20Ni80, were borided at 850°C for 8 h using a high boron potential powder medium. On both alloys ~150 μm thick boride coatings grew in the form of two stratified sublayers of different thickness depending on the Ni content of the metal substrate. The outer sublayer mainly consisted of a ternary (Fe,Ni)B compound with small amounts of Ni borides in its outermost region, the inner by a ternary (Fe,Ni)2B compound. It is shown and explained how the same (Fe,Ni)B compound could form on both high-Ni alloys in spite of the considerable difference in Ni content.

Mechanical properties of rapidly solidified Fe–Al–B ternary alloys

In this work, the influence of Al and B concentration on the constituent phases and the mechanical properties of Fe 100− x− y Al x B y (0 < x ≤ 35, 0 < y ≤ 25, and x + y ≤ 50) ternary alloys produced by copper mould casting was investigated. In this composition range, the rapidly solidified alloys contain two crystalline phases: α-Fe(Al) solid solution and Fe 2B compound. Contour maps of compressive strength ( σ c) and fracture strain ( ɛ f) are plotted according to the quasi-static compression test results of the as-cast Fe–Al–B rods. These rapidly solidified Fe–Al–B crystalline alloys, such as Fe 55Al 30B 15 as a typical sample, can show an ultra-high σ c up to ∼3 GPa and a certain plasticity (∼5%). The formation of ultrafine eutectics and solid-solution strengthening of Al substitutional solution in α-Fe are considered to be responsible for the considerable improvement of strength.

The elasticity, bond hardness and thermodynamic properties of X 2B (X=Cr, Mn, Fe, Co, Ni, Mo, W) investigated by DFT theory

The first principles calculations are performed to investigate the elastic constants and thermodynamic parameters of X 2B compounds. The calculated elastic constants for these borides indicate that they are mechanically stable structures. The bulk modulus of them range from 230 to 310 GPa and the largest bulk modulus value is attributed to W 2B. Furthermore, the scale relation between C 44 and bulk modulus is observed in our case. Heat capacity is calculated based on Debye's quasi-harmonic approximation, and we decomposed the heat capacity into two contributions to find that electron excitations dominated the heat capacity at low temperatures. The hardness of X–B and B–B bonds is calculated using a semi empirical hardness theory.

Effect of composition and milling parameters on the critical ball milling of Ti–Si–B powders

The absence of brittle phases and elevated temperature during ball milling of a powder mixture containing a large amount of ductile component can contribute to reach an excessive agglomeration denoting a critical ball milling (CBM) behavior. This work reports in the effect of composition and milling parameters on the CBM behavior of Ti–Si–B powders. High-purity elemental Ti–Si–B powder mixtures were processed in a planetary ball mill in order to prepare the Ti 6Si 2B compound and two-phase Ti + Ti 6Si 2B alloys. TiH 2 chips instead of titanium powder were used as a starting material. To avoid elevated temperature in the vials during ball milling of Ti–Si–B powders the process was interrupted after each 10 min followed by air-cooling. Following, the milled powders were hot-pressed at 900 °C for 1 h. Samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometry (EDS). Short milling times followed by air-cooling contributed to obtain a large amount of powders higher than 75% in the vials. Only Ti and TiH 2 peaks were observed in XRD patterns of Ti–Si–B and TiH 2–Si–B, respectively, suggesting that extended solid solutions were achieved. The large amount of Ti 6Si 2B and Ti + Ti 6Si 2B structures were formed during hot pressing from the mechanically alloyed Ti–Si–B and TiH 2–Si–B powders.

Calculation of the electronic structure and hyperfine fields for Fe1 − x CoxB and (Fe1 − x Cox)2B compounds by the Korringa-Kohn-Rostoker method

The magnetic properties of Fe1 − xCoxB and (Fe1 − xCox)2B disordered compounds were investigated using first-principles calculations of the electronic structure in the framework of the density functional theory with the Korringa-Kohn-Rostoker method. The concentration dependences of the magnetic moments and the electron density were calculated for the Fe1 − xCoxB solid solutions. The results obtained were used to analyze in detail and to interpret the transition from a magnetic phase to a nonmagnetic phase, which was previously revealed from the experiments in the compounds under investigation. The performed analysis of the calculated hyperfine fields induced by the electronic shells at the iron and cobalt atoms in the (Fe1 − xCox)2B borides made it possible to explain the experimentally observed magnetic anisotropy.

Magnetic behavior of Co and Ni in pseudoternary boron compounds

The magnetic properties of YA 4− x M x B with A=cobalt (Co) or nickel (Ni) and M=Al or Cu were analyzed. Solid solutions are formed for x⩽1.5 when M=Cu and x⩽2 for M=Al. The magnetizations and Curie temperatures decrease as result of substitutions. The YCo 2Al 2B compound is paramagnetic. Band structure calculations were performed on the above systems. Finally, the magnetic behaviors of Co and Ni in YA 4− x M x B compounds is analyzed.

Crystal structure and magnetism of YPt 2B

The new ternary YPt 2B compound was synthesized by arc-melting, followed by annealing at 1370 K. The structure was refined down to R = 0.0408, wR 2 = 0.0692 from single crystal X-ray diffraction data (CAD-4 diffractometer, Mo Kα, 269 reflections with I > 2 σ( I o)) and to R F = 0.0539, R B = 0.0970 from X-ray powder diffraction for 77 reflections. YPt 2B was found to crystallize with a CePt 2B structure type, P6 222 space group (no. 180) ( a = 5.2977(1) Å, c = 7.8875(2) Å, Z = 3, V = 191.715(8) Å 3, ρ = 12.752 g cm −3). Magnetization and AC-susceptibility measurements indicate that there is no magnetic or superconducting transition in YPt 2B down to 2 K.