In vitro and in silico study of Aloe vera leaf extract against human breast cancer

Abstract

Aloe vera leaf contains some bioactive compounds that have a strong binding affinity toward estrogen receptor as compared to standard drug tamoxifen. In this study, we have found that the IC₅₀ of Aloe vera leaf extract against breast cancer cell line (MCF-7) is 23?µg/mL which is much lower than the IC₅₀ (332?µg/mL) of Aloe vera leaf extract against non-cancerous cell line (NIH-3T3). We have also calculated the total concentration of phenolic acid (385.662?µg/mL), flavonoids (160.402?µg/mL) and alkaloids (276.754?µg/mL) in Aloe vera leaf extract. The free radical scavenging activity of Aloe vera leaf extract is 67% to 89% (at 50 to 300?µg/ml). Our virtual molecular docking study suggests that bioactive compounds like Aloe-emodin (?8.8?Kcal/mol), 7-hydroxy-2,5 dimethylchromone (?7.5?Kcal/mol), Beta-sitosterol (?7.3?Kcal/mol) etc. have a greater binding affinity toward estrogen alpha receptor as compared to standard drug Tamoxifen (?6.4?Kcal/mol).

     

Simple methods for the direct assembly, functionalization, and patterning of acid-terminated monolayers on Si111

This article describes mild methods to directly assemble, functionalize, and pattern monolayers of undecylenic acid on hydrogen-terminated Si(111). These monolayers were assembled under very mild conditions from a neat solution of undecylenic acid containing 0.1 mol % 4-(decanoate)-2,2,6,6-tetramethylpiperidinooxy at room temperature without the need for UV light. Because of these mild conditions, monolayers exposing carboxylic acids could be assembled in one step without the need to protect the acid prior to its assembly. The monolayers were extensively characterized by horizontal attenuated total reflection infrared spectroscopy, X-ray photoelectron spectroscopy (XPS), and contact angle goniometry. The monolayers bonded to the silicon surface preferentially through the olefin with no detectable bonds between the carboxylic acids and silicon. The crystallinity of the monolayer was studied by infrared spectroscopy through the antisymmetric--v(a)(CH(2))--and symmetric--v(s)(CH(2))--stretches for methylene. Because it is important for future applications to assemble functional surfaces, methods to react the acid-terminated monolayers with trifluoroacetic anhydride and triethylamine to yield a symmetric anhydride on the monolayer were studied. These anhydrides were reacted with a variety of milligram-quantity amines to yield amide-terminated surfaces. This method was general, and a variety of amines could be bonded to the monolayer. The stabilities of these monolayers upon exposure to ambient conditions and under a variety of solvents were described. Because patterned monolayers have found wide applications, we have developed methods to pattern 1-octadecylamine and poly(ethylenimine) on the micrometer scale using soft lithography. In addition, polymer brushes of polynorbornene with thicknesses from 32 to 150 nm were grown from monolayers patterned with the Grubbs' catalyst. The patterned surfaces were imaged by scanning electron microscopy, scanning probe microscopy, and ellipsometry to determine the thicknesses of the patterns and the fidelity of the method.     

A Facile One‐Pot Route for the General Synthesis of Triazole Linked Chiral 2‐Substituted Benzimidazoles

One‐pot protocol for the synthesis of novel class of triazole linked 2‐sugar and 2‐aryl substituted benzimidazoles has been developed. The rapid and simple method involves copper (I) catalyzed simultaneous formation of benzimidazole and triazole rings at room temperature and in high yield.     

Atomic Layer Deposited Ti2O3 Thin Films

Ti₂O₃ thin films have been prepared through atomic layer deposition and subjected to electrical resistivity measurements as a function of temperature. The as-prepared films were stable for up to three weeks. In Ti₂O₃ thin films, the insulator-metal transition is observed at ∼80 K, with nearly 3–4 orders of magnitude change in resistivity. The anomalous increase in electrical resistivity in the films is in accordance with the two-band model. However, the energy interval between the bands depending on the crystallographic c/a ratio leads to a change in electrical resistivity as a function of temperature.     

A simple mathematical model for seasonal planktonic blooms

We show how the inclusion of the defense strategy by different species can alter the prediction of simple models. One of the defense strategy by the phytoplankton population against their grazer is the release of toxic chemicals. In turn the zooplankton population reduces there predation rate over toxin producing phytoplankton (TPP) to protect themselves from those toxic chemicals. Thus, when the level of toxicity is high, the grazing pressure is low and when the level of toxicity is low or when the toxin is absent, the grazing pressure is high. Here we have considered a TPP–zooplankton system where the rate of toxin liberation and the predation rate vary with zooplankton abundance. We observe that our proposed model has the potential to show different dynamical behaviour that are similar to that seen in real‐world situations. Further, we consider three different functional forms for the distribution of the toxins and compare them using latin hypercube sampling technique and found that the functional forms seem to have no effect in determining the final outcome of the system. Copyright © 2009 John Wiley & Sons, Ltd.     

Kinetics of Surfactant-induced Aggregation of Lysozyme Studied by Fluorescence Spectroscopy

The study of protein conformational changes in the presence of surfactants and lipids is important in the context of protein folding and misfolding. In the present study, we have investigated the mechanism of the protein conformational change coupled with aggregation leading to size growth of Hen Egg White Lysozyme (HEWL) in the presence of an anionic detergent such as sodium dodecyl sulphate (SDS) in alkaline pH. We have utilized intrinsic protein fluorescence (tryptophan) and extrinsic fluorescent reporters such as 8-anilinonaphthalene-1-sulfonic acid (ANS), dansyl and fluorescein to follow the protein conformational change in real-time. By analyzing the kinetics of fluorescence intensity and anisotropy of multiple fluorescent reporters, we have been able to delineate the mechanism of surfactant-induced aggregation of lysozyme. The kinetic parameters reveal that aggregation proceeds with an initial fast-phase (conformational change) followed by a slow-phase (self-assembly). Our results indicate that SDS, below critical micelle concentration, induces conformational expansion that triggers the aggregation process at a micromolar protein concentration range.     

Fast enzyme dynamics at the active site of formate dehydrogenase

The role of femtosecond-picosecond structural dynamics of proteins in enzyme-catalyzed reactions is a hotly debated topic. We report infrared photon echo measurement of the formate dehydrogenase-NAD+-azide ternary complex. In contrast to earlier studies of protein dynamics, the data show complete spectral diffusion on the femtosecond-picosecond time scale with no static heterogeneity. This result indicates that this transition-state analogue complex completely samples the distribution of structures that determine the distribution of azide vibrational frequencies within a few picoseconds and that there are no slower motions that perturb the H-bond network at the active site.     

Bile-Acid-Appended Triazolyl Aryl Ketones: Design,Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as ¹H and ¹³C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate 6cf to be most active against both cancer cell lines, with IC₅₀ values of 5.71 µM and 8.71 µM, respectively, as compared to the reference drug docetaxel, possessing IC₅₀ values of 9.46 µM and 13.85 µM, respectively. Interestingly, another compound 6af (IC₅₀ = 2.61 µM) was found to possess pronounced anticancer activity as compared to the reference drug docetaxel (IC₅₀ = 9.46 µM) against MCF-7. In addition, the potent compounds (6cf and 6af) were found to be non-toxic to normal human embryonic kidney cell line (HEK 293), as evident from their cell viability of greater than 86%. Compound 6cf induces higher apoptosis in comparison to 6af (46.09% vs. 33.89%) in MCF-7 cells, while similar apoptotic potential was observed for 6cf and 6af in 4T1 cells. The pharmacokinetics of 6cf in Wistar rats showed an MRT of 8.47 h with a half-life of 5.63 h. Clearly, these results suggest 6cf to be a potential candidate for the development of anticancer agents.     

Interplay of structural dynamics and electronic effects in an engineered assembly of pentacene in a metal–organic framework

Charge carrier mobility is an important figure of merit to evaluate organic semiconductor (OSC) materials. In aggregated OSCs, this quantity is determined by inter-chromophoric electronic and vibrational coupling. These key parameters sensitively depend on structural properties, including the density of defects. We have employed a new type of crystalline assembly strategy to engineer the arrangement of the OSC pentacene in a structure not realized as crystals to date. Our approach is based on metal–organic frameworks (MOFs), in which suitably substituted pentacenes act as ditopic linkers and assemble into highly ordered π-stacks with long-range order. Layer-by-layer fabrication of the MOF yields arrays of electronically coupled pentacene chains, running parallel to the substrate surface. Detailed photophysical studies reveal strong, anisotropic inter-pentacene electronic coupling, leading to efficient charge delocalization. Despite a high degree of structural order and pronounced dispersion of the 1D-bands for the static arrangement, our experimental results demonstrate hopping-like charge transport with an activation energy of 64 meV dominating the band transport over a wide range of temperatures. A thorough combined quantum mechanical and molecular dynamics investigation identifies frustrated localized rotations of the pentacene cores as the reason for the breakdown of band transport and paves the way for a crystal engineering strategy of molecular OSCs that independently varies the arrangement of the molecular cores and their vibrational degrees of freedom.

Pentacene assembled into 1D arrays using a metal–organic framework (MOF) approach. This cofacial packing motif, which is not present in pentacene bulk, shows an interesting interplay of band-like and hopping-type transport.