Stereoselective Synthesis of the Di-Spirooxindole Analogs Based Oxindole and Cyclohexanone Moieties as Potential Anticancer Agents

A new series of di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were synthesized. Initially, azomethine ylides were generated via reaction of the substituted isatins 3a–f (isatin, 3a, 6-chloroisatin, 3b, 5-fluoroisatin, 3c, 5-nitroisatin, 3d, 5-methoxyisatin, 3e, and 5-methylisatin, 3f, and (2S)-octahydro-1H-indole-2-carboxylic acid 2, in situ azomethine ylides reacted with the cyclohexanone based-chalcone 1a–f to afford the target di-spirooxindole compounds 4a–n. This one-pot method provided diverse structurally complex molecules, with biologically relevant spirocycles in a good yields. All synthesized di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were evaluated for their anticancer activity against four cancer cell lines, including prostate PC3, cervical HeLa, and breast (MCF-7, and MDA-MB231) cancer cell lines. The cytotoxicity of these di-spirooxindole analogs was also examined against human fibroblast BJ cell lines, and they appeared to be non-cytotoxic. Compound 4b was identified as the most active member of this series against prostate cancer cell line PC3 (IC₅₀ = 3.7 ± 1.0 µM). The cyclohexanone engrafted di-spirooxindole analogs 4a and 4l (IC₅₀ = 7.1 ± 0.2, and 7.2 ± 0.5 µM, respectively) were active against HeLa cancer cells, whereas NO₂ substituted isatin ring and meta-fluoro-substituted (2E,6E)-2,6-dibenzylidenecyclohexanone containing 4i (IC₅₀ = 7.63 ± 0.08 µM) appeared to be a promising agent against the triple negative breast cancer MDA-MB231 cell line. To explore the plausible mechanism of anticancer activity of di-spirooxindole analogs, molecular docking studies were investigated which suggested that spirooxindole analogs potentially inhibit the activity of MDM2.     

C-hexylpyrogallol[4]arene and β-cyclodextrin as directors of the mode of binding of Coumarin 153 with DNA

The supramolecular interaction between calf thymus DNA (ctDNA) and Coumarin 153 in the presence of β-cyclodextrin (β-CD) or C-hexylpyrogallol[4]arene (C-HPA) was studied. Inclusion complexes of Coumarin 153 with β-CD and C-HPA were characterised by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and two-dimensional rotating-frame nuclear overhauser effect spectroscopy. The inclusion complexation was further followed by steady-state and time-resolved fluorescence measurements. The influence of β-CD or C-HPA in the binding strength and binding model of C153 with ctDNA was studied by UV–visible, fluorescence and molecular modelling technique. The possible group of interaction of Coumarin 153 with DNA, β-CD and C-HPA was shown by molecular modelling technique.     

Electrodeposition of cobalt with tunable morphology from reverse micellar solution

Electrodeposition of cobalt on a copper electrode was successfully performed from aqueous and reverse micellar solutions of a cationic surfactant, cetyltrimethylammonium bromide (CTAB), using constant potential electrolysis method. The potential to be applied for electrodeposition was judged from the cyclic voltammetric behavior of cobalt(II) in aqueous and reverse micellar solutions of CTAB at different compositions. The morphology, dimension, and crystallinity of cobalt deposited onto a copper substrate were evaluated from scanning electron microscopy (SEM) images and X-ray diffraction technique. The cobalt deposited on copper from aqueous solution does not show any definite shape and size, while the deposition from reverse micellar solutions occurred with definite shapes such as star-, flower-, and nanorod-like structures depending on the composition. The slow kinetics governed by the reverse micelles associated with the deposition brings about oriented growth of cobalt onto the copper substrate and offers the potential to electrochemically tune cobalt deposit with desirable morphology.     

2,4,6-Trichloro-1,3,5-triazine (TCT) mediated one-pot sequential functionalisation of glycosides for the generation of orthogonally protected monosaccharide building blocks

Orthogonally protected monosaccharide building blocks have been prepared using TCT in a one-pot multicomponent transformation. The process involves successive steps of arylidene acetalation, esterification and regioselective reductive acetal cleavage. High regioselectivity, scope for using a broad range of substrates, functional group tolerance, mild reaction conditions, easy handling process and wide application range are a few advantages of the current process.     

Transparent monolithic cubic mesoporous silica synthesized by structure-directing surfactant

The synthesis of transparent monolithic silica with a structure consistent with a space group Pn3m )isdemonstratedusingatemplate-directedsynthesisapproach.TheprocedureisbasedonthehydrolysisandpolymerizationofsiliconalkoxideatlowpHinthepresenceofacationicsurfactant.Thelow-pHreactionrouteischosentoobtaintransparentmonolithicmesoporoussilica.AstructureconsistentwiththePn3m) space group with unit cell lattice parameter ranging from 60–64 Å was identified using small-angle X-ray diffraction. While the lattice parameter is observed to be a monotonically increasing function of surfactant-to-silica ratio, the surfactant-to-alkoxide ratio has a weak discernible effect on the lattice parameter. The Brunauer, Emmett, and Teller (BET) surface area, total pore volume and average pore diameter of the samples are in the range of 787–845 m²/g, 0.37–0.51 cc/g and 18–24 Å respectively. This synthesis approach offers a one-step formation of monolithic mesoporous silica of diverse dimensions for potential use in a variety of technological applications such as catalysis, controlled release and adsorption phenomena . PACS 36.10.Gr; 68.65.-k; 73.21.-b; 73.23.-b     

β-Cyclodextrin Inclusion Complexes of 2-Hydroxyfluorene and 2-Hydroxy-9-fluorenone: Differences in Stoichiometry and Excited State Prototropic Equilibrium

We report that 1:1 and 1:2 complexes are formed for 2-hydroxy-9-fluorenone with β-cyclodextrin (β-CD) and that there is an unusual red shift in emission at higher concentrations of β-CD. Between different stoichiometries of the complexes the titrimetric curves for the neutral–anionic equilibria for the guests differ drastically and so do the excited state pK values. The formation of an 1:1 inclusion complex with 2-hydroxy-9-fluorenone (2HFN) as the guest in β-CD with the binding constant (K) of 606.65 L·mol^?1 was determined. The ground and excited state pK _a values for the neutral–mono-anion equilibrium are not affected by β-CD. Hence the hydroxyl group is considered exposed in the aqueous environment. Two different types of inclusion complexes of 2HFN were observed in β-CD. The 1:2 complex of 2HFN shows a red shift from the 1:1 complex and is less fluorescent that the 1:1 complex. The red shift reveals that the 1:2 complex is more stabilized than the 1:1 complex. The excited state pK _a values in both complexes with β-CD are higher that those in aqueous solution. This shows that the complexation makes the molecule less acidic in the S1 state. The β-CD molecule is perceived as not able to encapsulate the 2HFN molecule fully, but the larger rim of the β-CD comes closer to the C=O group. The other half of the 2HFN molecule is encapsulated by the second β-CD molecule and thus there is formation of the 1:2 inclusion complex at higher concentrations of β-CD.     

Generalized equilibrium and fixed point problems for Bregman relatively nonexpansive mappings in Banach spaces

In this paper, we introduce and study a hybrid iterative method for finding a common solution of a generalized equilibrium problem and a fixed point problem for a Bregman relatively nonexpansive mapping in reflexive Banach spaces. We prove that the sequences generated by the hybrid iterative algorithm converge strongly to a common solution of these problems. Further, we give some consequences of the main result. Finally, we discuss a numerical example to demonstrate the applicability of the iterative algorithm.     

Effect of cationic and anionic surfactants on the addition–elimination-type interaction between o-toluidine and d-glucose

The kinetics of the o-toluidine–d-glucose reaction has been studied as a function of [o-toluidine], [d-glucose], [acetic acid], and temperature by UV–visible spectrophotometry at 630 nm in the absence and presence of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS). The reaction follows second-order kinetics, being unity in each of the reactants in both media. The effect of added surfactants has also been investigated. The model of micellar catalysis, such as the Menger–Portony model modified by Bunton, is applied to explain the catalytic role of CTAB and SDS micelles. The association/incorporation constants (K _s and K _n), the rate constant in micellar media (k _m), and the activation parameters of this system have been calculated and discussed. The value of the rate constant is found to be higher in SDS than in CTAB. Hydrophobic and electrostatic interactions are responsible for higher reaction rates in SDS. From all observed facts, a reaction mechanism involving a nucleophilic addition–elimination path has been suggested.