Compound B2 Research Articles

Synthesis and properties of novel organogelators functionalized with 5-iodo-1,2,3-triazole and azobenzene groups

Two series of 5-iodo-1,2,3-triazole derivatives containing azobenzene group(s) were synthesized and their gelling properties were tested. Those containing two azobenzene groups (B series) have better gelation performance than those containing one azobenzene group (A series). The microstructure of organogels and the driving force of gelation were investigated by scanning electron microscopy and 1H NMR, respectively. It was found that π-π stacking, van der Waals interaction, and dipole-dipole interaction were the main forces of gelation. All the tested organogels are photoresponsive and those from B series are smarter than that from A series. Henry δp-δh diagrams of compounds A1, A2, and B2 were constructed on the basis of their gelation performance and the Hansen solubility parameters of related solvents. The constructed Henry δp-δh diagrams can be used to estimate the behavior of three compounds in any untested solvent. Open image in new window

New isothiocyanatotolane liquid crystals with terminal but-3-enyl substitute

ABSTRACTFour kinds of new but-3-enyl-based isothiocyanate liquid crystals composed of tolane core and but-3-enyl terminal group (A1–A4) were synthesised via seven step reactions based on 2-(4-bromophenethyl)-1,3-dioxolane, and four n-butyl analogues B1–B4 as comparison structures were also prepared. The mesomorphic properties and physical properties of the compounds were investigated. Single fluorinated compounds A2 and A3 exhibit monotropic nematic phase, and they have lower melting enthalpy and higher clearing points than those of the comparison compounds B2 and B3. The non-fluoro-substituted compound A1 and difluorinated compound A4 exhibit no nematic phase. Replacement of n-butyl chain by but-3-enyl as terminal group is enabled to increase birefringence (Δn ~ 0.394–0.430) and reduce rotational viscosity. These isothiocyanatotolanes with terminal but-3-enyl substitution have potential application for high birefringence mixtures.

Design, synthesis, docking studies and biological evaluation of novel dihydro-1,3,5-triazines as human DHFR inhibitors

A novel series of dihydro-1,3,5-triazine derivatives bearing a heteroatom spiro-ring were designed and synthesized on the basis of molecular flexible docking work, and their biological activities were evaluated. Compounds A2, A5, B1 and B3 showed potent human dihydrofolate reductase (hDHFR) inhibitory activity with IC50 values of 7.46 nM, 3.72 nM, 6.46 nM, 4.08 nM, versus reference drug methotrexate (MTX). From the molecular docking result we concluded that the conformation space generated by deformation of the flexible residue Phe31 is favorable for the binding of the spiro-ring, and inserting heteroatom into spiro ring might increase the binding affinity. There were 24 compounds with broadspectrum antiproliferative activity against several tumor cell lines (HCT116, A549, HL-60, HepG2 and MDA-MB-231) with IC50 values ranging from 0.79 to 0.001 μM. The antitumor activity in vivo of compound A2 was determined in a human alveolar basal epithelial cell line A549 xenograft model. This study offered novel anticancer agents with high inhibitory activity that target hDHFR and have a binding mode of the novel molecular scaffold with hDHFR. This provides potent support for further development of novel hDHFR inhibitors.

Polymorphism in chloro derivatives of 1,4-naphthoquinone: Experiment and density functional theoretic investigations

Molecular interactions underlying polymorphs of chlorine containing 1,4-naphthoquinone derivatives have been investigated by employing single crystal X-ray, 1H NMR, FTIR and electronic spectra experiments combined with density functional theory. Two polymorphs of 2,3-dichloro-1,4-naphthoquinone possessing (i) triclinic space group P-1(A1 and A3), and (ii) orthorhombic with Pb21a (A2) space group were obtained. The polymorph A3 has two molecules in its asymmetric unit which facilitate CH⋯O interactions engendeing polymeric planar sheets. The two polymorphs of 2-amino-3-chloro-1,4-naphthoquinone reveal monoclinic forms with Pc (B1) and C2/C (B2) space groups. A tetramer of B2 molecule possess NH⋯O interactions. The polymorphs of 2-chloro-3-hydroxy-1,4-naphthoquinone crystallizes in monoclinic space groups Pc (C1) and Pn (C2). Polymeric chain of C2 molecules results via OH⋯O interactions and the chains further are connected through CH⋯Cl and π-π stacking interactions those arise from benzenoid and quinonoid centroid. Moreover A3 facilitates the dimer via the halogen bonding interactions. Furthermore hydrogen bonding renders stability to the dimer C2. On the other hand compound B2 does not favor dimer formation. These inferences based on experimental observations are rationalized through the use of the dispersion corrected M06-2x functional based density functional theory. Further time dependent density functional theory has been used to assign the electronic transitions in UV–visible spectra of A3, B2 and C2.

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen–Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods.

The boron-boron triple bond in NHC→B[triple bond, length as m-dash]B←NHC.

Quantum chemical calculations of the compound B2(NHCMe)2 and a thorough examination of the electronic structure with an energy decomposition analysis provide strong evidence for the appearance of boron-boron triple bond character. This holds for the model compound and for the isolated diboryne B2(NHCR)2 of Braunschweig which has an even slightly shorter B-B bond. The bonding situation in the molecule is best described in terms of NHCMe→B2←NHCMe donor-acceptor interactions and concomitant π-backdonation NHCMe←B2→NHCMe which weakens the B-B bond, but the essential features of a triple bond are preserved. An appropriate formula which depicts both interactions is the sketch NHCMe⇄B[triple bond, length as m-dash]B⇄NHCMe. Calculations of the stretching force constants F BB which take molecules that have genuine single, double and triple bonds as references suggest that the effective bond order of B2(NHCMe)2 has the value of 2.34. The suggestion by Köppe and Schnöckel that the strength of the boron-boron bond in B2(NHCH)2 is only between a single and a double bond is repudiated. It misleadingly takes the force constant F BB of OBBO as the reference value for a B-B single bond which ignores π bonding contributions. The alleged similarity between the B-O bonds in OBBO and the B-C bonds in B2(NHCMe)2 is a mistaken application of the principle of isolable relationship.

Syntheses and anti-cancer activities of derivatives of tetrandrine and fangchinoline

A series of derivatives of tetrandrine and fangchinoline was designed and synthesized to find more active anti-cancer compounds. Their anti-cancer activities were tested against human hepatocellular carcinoma BEL-7402 and PLC/PRF/5 cells, human lung adenocarcinoma A549 cells as well as human leukaemia K562 cells, and the structure-activity relationship(SAR) was also studied. All the compounds except B1 exhibited superior inhibitory activities against PLC/PRF/5 cells with half maximal inhibitory concentration(IC50) values of less than 15 μmol/L, and compounds A2, A4, B2 and B4 showed IC50 values of less than 9 μmol/L. Compounds A2, A6, B2 and B4 showed potent anti-cancer activities against all the tested cells with IC50 values of less than 10 μmol/L. The results show that terandrine and fangchinoline derivatives are potential suppressors to human cancer.

Design, Synthesis and Cytotoxic Evaluation of Novel Imatinib Amide Derivatives that Target Abl Kinase

Novel imatinib amide derivatives (a1-28, b1-9) were synthesized and evaluated for their biological activities. All compounds were characterized by 1H NMR, MS and elemental analysis. Among all the derivatives, compounds a4, a10, a21, b1 and b2 displayed the most significant ability of inhibiting K562 cell proliferation with the IC50 values of 0.67, 0.66, 0.65, 0.59 and 0.62 µM, respectively, indicating that these compounds were potent inhibitors of Bcr-Abl in leukemic K562 cells, comparable to the reference compound imatinib. Molecular docking study was performed to position compounds a21 and b1 into the active site of Abl to determine the probable binding modes. Keywords: Amide derivatives, Bcr-Abl inhibitors, chronic myeloid leukemia, imatinib, inhibiting activity, molecular docking, SAR.

Synthesis, insecticidal activities and SAR of novel phthalamides targeting calcium channel

In order to find novel and environmental friendly insecticides targeting the ryanodine receptor, three series of novel phthalamides containing heptafluoroisopropyl group, low fluorine atoms group and non-fluorine group were designed and synthesized. 35 novel structures of three series were obtained. Insecticidal activities of title compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of title compounds showed moderate to high activities at the tested concentration. The structure–activity relationship (SAR) was discussed in detail. During synthesizing title compounds B8, C7, D1, D9 and D12, their corresponding positional isomers (B8′, C7′, D1′, D9′ and D12′) were afforded, and their structures were confirmed by 2D NMR. The calcium-imaging technique was also applied to investigate the effects of compounds B2, B10, C4 and C5 on the intracellular calcium ion concentration ([Ca2+]i), which indicated that they released stored calcium ions from endoplasmic reticulum, which denoted that some compounds are potential modulators of the insect ryanodine receptor (RyR).

Theoretical studies on two novel series of energetic cyclic nitramines

Density functional theory calculations at the B3LYP/6-31G** theoretical level were performed for two series of guanidine-fused bicyclic skeleton derivatives (B-B7 and C-C7). The heats of formation (HOFs) were calculated via isodesmic reaction; the detonation properties were evaluated using the Kamlet–Jacobs equations; the bond dissociation energies were also analyzed to investigate the thermal stability of the cyclic nitramines. The results show that all the derivatives have high positive HOFs; compounds containing –N3 groupshave the highest HOFs, while compounds containing –NF2 groups have the highest density and detonation properties. Taking both of the detonation properties and thermal stabilities into consideration, compounds B1, B2, B5, C3, and C5 can be considered as the potential candidate of high-energy density compounds.

Lettucenin sesquiterpenes contribute significantly to the browning of lettuce.

Wound-induced changes in the composition of secondary plant compounds cause the browning of processed lettuce. Cut tissues near the lettuce butt end clearly exhibit increased formation of yellow-brown pigments. This browning reaction is typically been attributed to the oxidation of polyphenols by the enzyme polyphenol oxidase (PPO). However, in our previous study on Iceberg lettuce, we showed that, besides the enzymatic polyphenol browning, other reactions must be involved in the formation of colored structures. With the present study for the first time, we isolated yellow sesquiterpenes by multilayer countercurrent chromatography (MLCCC), followed by preparative high-performance liquid chromatography (HPLC). Further analyses by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques identified lettucenin A and three novel derivatives. We call these compounds lettucenins A1, B, and B1. Color-dilution analyses revealed these lettucenins as key chromophores in the browning of Iceberg lettuce. A time formation curve showed the accumulation of lettucenins A and B within 40 h after cutting. Thereafter, these structures were degraded to unknown colored compounds. Lettucenin A was verified in five varieties of Lactuca. In contrast to that, lettucenin A was present only at trace levels in five varieties of Cichorium. Therefore, lettucenin A might be used as a chemosystematic marker of the genus Lactuca.

On the structure of luminol sodium salts

The structures of Tamerit® (A) and Galavit® (B) pharmaceutical preparations have been solved by X-Ray single crystal and powder diffraction. These are luminol sodium salts possessing immunomodulatory and anti-inflammatory properties. It is shown that Tamerit® (A) is a hydrated salt, while Galavit® (B) is a mixture of two polymorphic modifications (B1 and B2) of anhydrous salt. Compound A is crystallized in a monoclinic system: a = 8.3429(4) A, b = 22.0562(11) A, c = 5.2825(2) A, β = 99.893(3)°, V = 957.59(8) A3, and Z = 4; sp. gr. P21/c. Compound B1 is crystallized in a monoclinic system: a = 14.7157(18), b = 3.7029(19), c = 16.0233(15) A, β = 116.682(13)°, V = 780.1(4) A3, and Z = 4; sp. gr. P21/c. Compound B2 is crystallized in an orthorhombic system: a = 27.7765(15) A, b = 3.3980(19) A, c = 8.1692(19) A, V = 771.0(5) A3, and Z = 4; sp. gr. Pna21. The absence of phase transitions between the B1 and B2 polymorphs has been established by differential scanning calorimetry.

Synthesis, structures and photophysical properties of boron–fluorine derivatives based on pyridine/1,8-naphthyridine

Three boron–fluorine complexes B1–B3 containing pyridine/1,8-naphthyridine were synthesized and structurally characterized. Compounds B1 and B2 exhibited strong fluorescence in solution and solid state. The solvent-dependent luminous properties and large Stokes shift in solution could be explained by intramolecular charge transfer, which is confirmed by time-dependent density functional theory calculation. The absolute quantum yield of B1 in powder form reached 0.48 because of inhibiting planar π⋯π stacking. Single-crystal X-ray diffraction analyses of B1 and B2 revealed that weak intermolecular C–H⋯F and H⋯π interactions hinder further stacking of π⋯π dimers, consequently preventing aggregation-induced quenching. Complex B3, composed of boron–dipyrromethene and 1,8-naphthyridine fluorophore, had potential applications as a pH ratiometric fluorescent sensor.

Synthesis and Evaluation of 2, 4, 5 - Trisubstituted and 1, 2, 4, 5 Tetrasubstituted Imidazole as Antimicrobial Agents

A series of 2,4,5-trisubstituted (A1-A15) and 1,2,4,5-tetrasubstituted (B1-B7) imidazole derivatives were synthesized by the reaction of Benzil, aldehyde, ammonium acetate, aromatic primary amines using catalyst tetrabutylammoniumbromide in isopropanol. Structures of these compounds were elucidated by spectral (IR, 1 H NMR) analysis. The newly synthesized compounds were screened for antifungal and antibacterial activities. The activity was measured in terms of zone of inhibition and compared with standard drug. Compounds A4,A7,A8,A10,A12,A14,A15,B1,B3,B5 and B6 have shown good antibacterial activity against std. Norfloxacin and Compound A2,A3,A6,A7,A9,A10,A14,A15,B2,B3,B4,B6 and B7 exhibited good antifungal activities against std. Clotrimazole, and other compound shows moderate activity.

SYNTHESIS AND EVALUATION OF SOME NOVEL 1, 3, 4-OXADIAZOLEDERIVATIVES FOR ANTIMICROBIAL AND ANTIDIABETIC ACTIVITIES

A series of 1, 3, 4-Oxadiazole derivatives have been synthesized and evaluated for antimicrobial and antidiabetic activities. The newly synthesized compounds have been characterized by IR, 1 H NMR and elemental analysis. All compounds have shown promising antimicrobial and antidiabetic activities when compared with standard drug ciprofloxacin and acarbose respectively. Compounds A2 ,B2 ,C1 ,D1 ,D2 ,E1 and E2 have shown promising antimicrobial activity while compounds A1 ,A2 ,B1 ,C1 ,D1 ,E1 and E2 have shown promising antidiabetic activity.

SYNTHESIS AND EVALUATION OF SOME NEW SULPHUR, NITROGEN AND OXYGEN CONTAINING HETEROCYCLE THIADIAZOLOTRIAZOLE FOR ANTIBACTERIAL, ANTIFUNGAL & ANTITUBERCULAR ACTIVITY

Thiadiazoles are synthesized by using aromatic acids and thiosemicarbazide. Schiff base reaction is followed and then thiadiazolotriazole derivatives are prepared by using hydrazine hydrate, isoniazid and unhydrous FeCl3. All the synthesized compounds were characterized by IR, 1H-NMR and CHN analyses. All the compounds were evaluated for antibacterial, antifungal & antitubercular activity. Compounds A1,B1, C1 and C4 have shown promising antibacterial activity, compounds A3, A4, B4, C2 and C4 have exhibited excellent antifungal activities, while compounds A2, A4, B2, B4, C2 and C4 showed anti-tubercular activity.

Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocin-induced cognitive deficits

BackgroundIn this study, benzothiazole-piperazine compounds were synthesized by condensing the functional groups of donepezil (DNP), FK-960, and sabeluzole, which are known to have therapeutic potential against Alzheimer's disease, with the aim of obtaining new and potent anti-Alzheimer agents. MethodsInitially, acetylcholinesterase/butyrylcholinesterase enzyme inhibition activities of the synthesized test compounds were investigated by Ellman's method. Effects of the compounds on a streptozotocin (STZ) model of Alzheimer's disease (SMAD) were investigated in rats. SMAD was established by intracerebroventricular (icv) injection of STZ (3mg/kg), bilaterally. The elevated plus maze, Morris water maze, and active avoidance tests were used to examine the effects of test compounds (1,5, and 10mg/kg) on learning and memory parameters of icv STZ-injected rats. Effects of the test compounds on spontaneous locomotor activities of rats were examined with the activity cage test. ResultsThe compounds B2–B5 and DNP exhibited significant selective inhibitory potencies against acetylcholinesterase. Compounds B2 and B3 at 10mg/kg doses and compounds B4 and B5 at 5 and 10mg/kg doses, as well as the reference drug DNP (1 and 3mg/kg), significantly improved the learning and memory parameters of animals in all cognition tests. None of the test compounds changed spontaneous locomotor activities. ConclusionResults of the present study revealed that compounds B2-B5 repaired the parameters related to the learning and memory deficits of icv STZ-injected rats. Potencies of these test compounds were comparable to the activity of DNP.

Identification of Novel and Selective KV2 Channel Inhibitors

Identification of selective ion channel inhibitors represents a critical step for understanding the physiological role that these proteins play in native systems. In particular, voltage-gated potassium (K(V)2) channels are widely expressed in tissues such as central nervous system, pancreas, and smooth muscle, but their particular contributions to cell function are not well understood. Although potent and selective peptide inhibitors of K(V)2 channels have been characterized, selective small molecule K(V)2 inhibitors have not been reported. For this purpose, high-throughput automated electrophysiology (IonWorks Quattro; Molecular Devices, Sunnyvale, CA) was used to screen a 200,000-compound mixture (10 compounds per sample) library for inhibitors of K(V)2.1 channels. After deconvolution of 190 active samples, two compounds (A1 and B1) were identified that potently inhibit K(V)2.1 and the other member of the K(V)2 family, K(V)2.2 (IC(50), 0.1-0.2 μM), and that possess good selectivity over K(V)1.2 (IC(50) >10 μM). Modeling studies suggest that these compounds possess a similar three-dimensional conformation. Compounds A1 and B1 are >10-fold selective over Na(V) channels and other K(V) channels and display weak activity (5-9 μM) on Ca(V) channels. The biological activity of compound A1 on native K(V)2 channels was confirmed in electrophysiological recordings of rat insulinoma cells, which are known to express K(V)2 channels. Medicinal chemistry efforts revealed a defined structure-activity relationship and led to the identification of two compounds (RY785 and RY796) without significant Ca(V) channel activity. Taken together, these newly identified channel inhibitors represent important tools for the study of K(V)2 channels in biological systems.

Synthesis, Characterization and Biological Evaluation of Platinum(II) Complexes with a Chiral N-Monosubstituted 1,2-Cyclohexyldiamine Derivative

Eight platinum(II) compounds with a new chiral ligand, 2-(((1R,2R)-2-aminocyclohexylamino)methyl)phenol (HL), were designed, prepared and spectrally characterized. All compounds showed better aqueous solubility than cisplatin and oxaliplatin. In vitro cytotoxicity of these compounds against human HepG-2, MCF-7, A549 and HCT-116 cell lines was evaluated. Results indicated that all compounds showed cytotoxicity against A549 and HepG-2 cell lines. Particularly, compounds B1 and B8, which have CF₃SO₃⁻ and (CH₃)₃COCH₂COO(-) as leaving groups, respectively, exhibited better cytotoxicitiy than that of carboplatin in these two cell lines.

The effect of deposition temperature on the intermixing and microstructure of Fe/Ni thin film

The physical vapour deposition of Ni atoms on α-Fe(001) surface under different deposition temperatures were simulated by molecular dynamics to study the intermixing and microstructure of the interfacial region. The results indicate that Ni atoms hardly penetrate into Fe substrate while Fe atoms easily diffuse into Ni deposition layers. The thickness of the intermixing region is temperature-dependent, with high temperatures yielding larger thicknesses. The deposited layers are mainly composed of amorphous phase due to the abnormal deposition behaviour of Ni and Fe. In the deposited Ni-rich phase, the relatively stable metallic compound B2 structured FeNi is found under high deposition temperature conditions.