Antioxidant activity and cytotoxic effect of aviprin and aviprin-3″-O-D-glucopyranoside on LNCaP and HeLa cell lines

Many researchers have shown that plant-derived polyphenolic compounds are helpful nutraceuticals in restraining various disorders such as neoplastic diseases. In this study two linear furanocoumarins, aviprin and aviprin-3″-O-D-glucopyranoside (A3G), were isolated from methanol extract of Prangos uloptera roots. The evaluation of free radical scavenging capacity of the compounds showed that aviprin is a more effective antioxidant than A3G with RC50 of 0.54?mg?mL?1. The biological and antiproliferative activities of the furanocoumarins were examined using human cervical carcinoma HeLa cell line and LNCaP prostatic cell line. Cell membrane integrity and cell viability were evaluated by measuring trypan blue exclusion assay and reduction of the tetrazolium blue compound, respectively. Treating the LNCaP cell line with various concentrations of the furanocoumarins showed that IC?? of aviprin and A3G were 0.4 and 6.6?mg?mL?1, whereas their CC50 values were 0.7 and 11?mg?mL?1, respectively. These results indicated that 42.7% of LNCaP cells were not dead by necrosis. Treating the HeLa cells by the furanocoumarins showed the greater sensitivity of the HeLa cell line than the LNCaP cell line. A morphological analysis and the study of DNA fragmentation provided further some evidence for the inhibition of the LNCaP cell line via apoptosis induction.     

Chemical composition of the essential oil from basil (Ocimum basilicum Linn.) and its in vitro cytotoxicity against HeLa and HEp-2 human cancer cell lines and NIH 3T3 mouse embryonic fibroblasts

This study examines the chemical composition and in?vitro anticancer activity of the essential oil from Ocimum basilicum Linn. (Lamiaceae), cultivated in the Western Ghats of South India. The chemical compositions of basil fresh leaves were identified by GC-MS: 11 components were identified. The major constituents were found to be methyl cinnamate (70.1%), linalool (17.5%), β-elemene (2.6%) and camphor (1.52%). The results revealed that this plant may belong to the methyl cinnamate and linalool chemotype. A methyl thiazol tetrazolium assay was used for in?vitro cytotoxicity screening against the human cervical cancer cell line (HeLa), human laryngeal epithelial carcinoma cell line (HEp-2) and NIH 3T3 mouse embryonic fibroblasts. The IC(50) values obtained were 90.5 and 96.3?μg?mL(-1), respectively, and the results revealed that basil oil has potent cytotoxicity.     

Synthesis of new 9-hydroxy-α- and 7-hydroxy-β-pyran naphthoquinones and cytotoxicity against cancer cell lines

A synthetic method to obtain α- and β-pyran naphthoquinones 10 and 11 with a hydroxyl substituent on the aromatic ring was developed. Two series of α- and β-pyran naphthoquinones were obtained from the 8-hydroxy-lawsone, and their anticancer properties were evaluated against four tumor cell lines. In general, the new compounds displayed good activity, possibly indicating that these compounds have increased pro-oxidant capacity. The 9-hydroxy-α-lapachone and 7-hydroxy-β-lapachone analogues of the natural products α-lapachone and β-lapachone were successfully produced by this methodology.     

In vivo biodistribution,antioxidant and hemolysis tendency of superparamagnetic iron oxide nanoparticles – Potential anticancer agents

Ferromagnetic and superparamagnetic oxide nanoparticles are of particular attention because of their possible use in various fields ranging from bio-nanotechnology to spintronics. Detailed magnetic, dielectric and impedance investigations are crucial for the above-mentioned applications. This study deals with the exploration of various iron oxide phases under as-synthesized conditions by sol–gel method. pH of the sols is varied in the range of 1 to 11. X-ray diffraction (XRD) analysis indicate amorphous behavior for nanoparticles synthesized using pH 1 and 3. Nanoparticles synthesized using pH 2 and 4–6 exhibit hematite phase of iron oxide. Whereas structural transition to maghemite phase is observed for pH 7–8. Nanoparticles synthesized using high pH values, i.e. 9–11, exhibit structural transition towards magnetite phase of iron oxide. Hematite nanoparticles exhibit superparamagnetic and ferromagnetic hysteresis curves with saturation magnetization of ～ 24 emu/g and ～ 13–17 emu/g at pH 2 and pH 4–6, respectively. Maghemite nanoparticles exhibit superparamagnetic (pH 7) and ferromagnetic (pH 8) response with saturation magnetization of ～ 69 and ～ 42 emu/g, respectively. Fe₃O₄ nanoparticles exhibit superparamagnetic (pH 9–10) and ferromagnetic (pH 11) behavior with saturation magnetization of ～ 88, 87 and 52 emu/g, respectively. High grain boundary resistance contributed towards high dielectric constant of ～ 99, 109 and 154 (log f = 5.0) at pH 2, 7 and 9. Detailed impedance values indicate dominant role of grain boundaries in the conductivity of iron oxide nanoparticles. Superparamagnetic iron oxide (pH 9) exhibits strong antioxidant activity along with a very weak hemolytic response. The findings of cell lysis reveal that synthesized nanoparticles have a potential to combat dangerous cancer cells. Drug efficacy results show that after 120 min the encapsulation efficacy reaches a peak of ～ 83 % using curcumin, a naturally existing drug. In vivo biodistribution of nanoparticles was studied in Rabbit model. Synthesized nanoparticles are labelled using Technetium-99 m. Whereas, labeling efficacy and stability was examined using =nstant thin layer chromatography (ITLC) process. In vitro and in vivo results suggest potential anti-cancer applications of as-synthesized superparamagnetic nanoparticles.     

An optical DNA logic gate based on strand displacement and magnetic separation,with response to multiple microRNAs in cancer cell lysates

A battery of logic gates, “YES”, “AND” and “OR”, are constructed using magnetic beads (MBs) modified by DNA which consists of a substrate strand (S) and a signal strand on which the logic operates. Inputs stemming from micro-RNA (which represent three cancer biomarkers) take the place of signal DNA. The released signal strand self-assembles into the hemin-G-quadruplex complex (DNAzyme) that catalyzes a blue-green dye (ABTS⁺) from the precursor ABTS. This dye (quantified at a wavelength of 414 nm) represents the output signal for the various logic gates. The method allows quantitative detection of microRNA of three kinds of logic gates in the range of 5 nM–500 nM with detection limits of 3.8 nM, 4.9 nM, 5.4 nM. Boolean logic circuitry is also achieved following the principles of multilevel strand displacement. Based on strand displacement and magnetic separation, this work demonstrates the possibility of designing a logic system using micro-RNA in live cell lysate as inputs, and its potential application in DNA computation and cancer diagnosis.

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Graphical abstract Schematic representation of a battery of logic gates and the Boolean logic circuitry based on strand displacement and magnetic separation responding to multiple microRNA in cancer cell lysate.

     

Physico-chemical comparison of betulinic acid, betulin and birch bark extract and in vitro investigation of their cytotoxic effects towards skin epidermoid carcinoma (A431), breast carcinoma (MCF7) and cervix adenocarcinoma (HeLa) cell lines

Betulin and betulinic acid are pentacyclic triterpenes present in the bark of the birch tree and other vegetal sources. Quantitatively, in birch bark betulin is more significant than betulinic acid; therefore, birch can be a large and feasible source of raw material for betulin extraction. Betulin can be used as extracted or, after chemical modification, as a starting compound for its acid, betulinic acid, with both substances possessing various interesting pharmacological properties. The purpose of this study is to analyse the betulin and betulinic acid content of a birch tree bark extract, as well as its cytotoxic activity. The extraction was done using a Soxhlet extractor and chloroform/dichlormethane/methanol (1?:?1?:?1) as solvent. The betulin and betulinic acid content of the extract was estimated using standards of pure betulin and betulinic acid, by thermal analysis as opposed to pure substance (thermogravimetric and differential thermal analysis). The extract and the main compounds were also analysed by NMR. The results indicated a high amount of betulin in the final extract (up to 50%), and an important quantity of betulinic acid: over 3%. The cytotoxic activity indicated a high proliferation inhibition for the birch tree extract but was still comparable with betulinic acid and betulin.     

New naphthalene derivative for cost-effective AChE inhibitors for Alzheimer’s treatment: In silico identification,in vitro and in vivo validation

Neurodegenerative diseases have complex etiology and pose a challenge to scientists to develop simple and cost-effective synthetic compounds as potential drug candidates for such diseases. Here, we report an extension of our previously published in silico screening, where we selected four new compounds as AChE inhibitors. Further, based on favorable binding possess, MD simulation and MMGBSA, two most promising compounds (3a and 3b) were selected, keeping in view the ease of synthesis and cost-effectiveness. Due to the critical role of BChE, LOX and α-glucosidase in neurodegeneration, the selected compounds were also screened against these enzymes.The IC₅₀ values of 3a against AChE and BChE found to be 12.53 and 352.42 μM, respectively. Moderate to slight inhibitions of 45.26 % and 28.68 % were presented by 3a against LOX and α-glucosidase, respectively, at 0.5 mM. Insignificant inhibitions were observed with 3b against the four selected enzymes. Further, in vivo trial demonstrated that 3a could significantly diminish AChE levels in the mice brain as compared to the control. These findings were in agreement with the histopathological analysis of the brain tissues. The results corroborate that selected compounds could serve as a potential lead for further development and optimization as AChE inhibitors to achieve cost-effective anti-Alzheimer’s drugs.     

Catalytic conversions of chloroolefines over iron oxide nanoparticles 3. Electronic and magnetic properties of γ-Fe2O3 nanoparticles immobilized on different silicas

Catalytic properties of superparamagnetic γ-ferric oxide nanoclusters, which are uniform in terms of size and magnetic properties were studied. The catalysts were supported on the activated silica gel matrix (AGM) prepared from the KSK-2 silica gel of globular structure and on the activated silica matrix (ASM) prepared from layered natural vermiculite. The clusters are active in some reactions of chloroolefin conversions: isomerization of dichlorobutenes and alkylation of benzene with allyl chloride. Their activity in these reactions is many times higher that of usual supported catalysts based on α-ferric oxide. Analysis of the Mössbauer spectra of the 2.5 wt.% Fe/AGM and 2.5 wt.%Fe/ASM samples before and after the reaction at T = 3–300 K shows that during the reaction some Fe^III ions arranged in ～2–3-nm γ-Fe₂O₃ nanoclusters magnetically ordered at 6 K are reduced to form a high-spin Fe^II complex in the paramagnetic state. According to the macroscopic magnetization data (SQUID) of the initial clusters, curves with hysteresis are observed at 2 K in the plots of forward and backward magnetization, while the 2.5 wt.%Fe/ASM catalyst after the reaction at T = 2 K demonstrates a linear field dependence of the magnetization passing through the coordinate origin. Analysis of the Mössbauer spectra and magnetic properties suggests that during the catalytic reaction the Fe^III ions in the γ-Fe₂O₃ nanoclusters interact with chloroolefin with the allylic structure to be partially reduced to the Fe^II ions that are bound in a complex containing chloride ions and O^II ion(s) of the silicate matrix as ligands. This is a reason, probably, for the high catalytic activity of γ-Fe₂O₃ nanoparticles.     

Phorbol Esters from Jatropha Meal Triggered Apoptosis, Activated PKC-δ, Caspase-3 Proteins and Down-Regulated the Proto-Oncogenes in MCF-7 and HeLa Cancer Cell Lines

Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood. Hence, this study was conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines. Isolated PEs inhibited cells proliferation in a dose-dependent manner of both MCF-7 and HeLa cell lines with the IC₅₀ of 128.6 ± 2.51 and 133.0 ± 1.96 μg PMA equivalents/mL respectively, while the values for the phorbol 12-myristate 13-acetate (PMA) as positive control were 114.7 ± 1.73 and 119.6 ± 3.73 μg/mL, respectively. Microscopic examination showed significant morphological changes that resemble apoptosis in both cell lines when treated with PEs and PMA at IC₅₀ concentration after 24 h. Flow cytometry analysis and DNA fragmentation results confirmed the apoptosis induction of PEs and PMA in both cell lines. The PEs isolated from Jatropha meal activated the PKC-δ and down-regulated the proto-oncogenes (c-Myc, c-Fos and c-Jun). These changes probably led to the activation of Caspase-3 protein and apoptosis cell death occurred in MCF-7 and HeLa cell lines upon 24 h treatment with PEs and PMA. Phorbol esters of Jatropha meal were found to be promising as an alternative to replace the chemotherapeutic drugs for cancer therapy.     

Let-7i miRNA and platinum loaded nano-graphene oxide platform for detection/reversion of drug resistance and synergetic chemical-photothermal inhibition of cancer cell

The drug resistance of chemotherapy is a major challenge to overcome for antineoplastic agents and the reverse of drug resistant is essential for cancer therapy. Herein, we developed a drug delivery system which can simultaneously detect/reverse the drug resistance and perform synergetic treatment of cancer. In this work, we integrated cyanine5(Cy5) modified mi RNA(let-7 i)(Cy5-mi RNA) and platinum onto nano-graphene oxide(NGO)(30-50 nm) platform to achieve simultaneously detection/reversion of ...     

“MCR-Click” synthesis of coumarin-tagged macrocycles with large Stokes shift values and cytotoxicity against human breast cancer cell line MCF-7

A three step “MCR-Click” strategy has been developed for the synthesis of a library of coumarin-tagged macrocycles with varying ring size from 11 to 18. The coumarin moiety connected to the peptidomimetic macrocycles thorough a keto-methylenic spacer helps the molecules to become optical systems with controlled emission properties. All the twelve macrocycles developed are emitting in the green region with high Stokes shift values indicating the potential of these molecules as probes for bioimaging applications. Similarly, the excellent cytotoxicity exhibited by the molecules toward human breast cancer cell line (MCF-7) further indicating the possibilities of these new macrocycles as potential anticancer/antitumor agents.     

Gabuda’s model of averaging local magnetic fields in solid-state NMR. The mobility of atoms and molecules

The review presents the main results of the studies of Prof. S. P. Gabuda, which were devoted to the NMR investigation of the mobility of atoms and molecules. The basic principles of his model for averaging local magnetic fields under the conditions of atomic and molecular mobility are outlined. This model provides a relationship between the parameters of these fields with the structural features of the mobility of atoms and molecules and intermolecular interactions. Ionic and molecular crystals, zeolites, molecular sieves, hydrated proteins, and so on are considered. Phase transitions in guest subsystems, effects of dynamic disordering and correlated electron motion on the mobility of atoms and molecules and their location are discussed.     

A multivariate insight into the in vitro antitumour screen database of the National Cancer Institute: classification of compounds, similarities among cell lines and the influence of molecular targets

A multivariate insight into the in vitro antitumour screen database of the NCI by means of the SIMCA package allows to propose hypotheses on the mechanism of action of novel anticancer compounds. As an example, the application of multivariate analysis to the NCI standard database provided clues to the classification of drugs whose mechanism is either unknown or controversial. Moreover, the influence of intrinsic biochemical cell line properties (molecular targets) on the sensitivity to drug treatment could be evaluated simultaneously for classes of compounds which act by the same mechanism. Interestingly, the present approach can also provide a correlation between the molecular targets and the therapeutical fingerprint of novel active compounds thus suggesting specific biochemical studies for the investigation of new mechanisms of drug action and resistance. The statistical approach reported here represents a valuable tool for handling theenormous data sets deriving from recent genome-wide investigations of gene expression in the NCI cell lines.     

Synthesis,characterization, photocleavage,cytotoxicity in vitro,apoptosis, and cell cycle arrest of ruthenium(II) complexes

Two new ruthenium(II) complexes, [Ru(dmp)₂(BHIP)]²⁺ (1) and [Ru(dmb)₂(BHIP)]²⁺ (2), were synthesized and characterized by elemental analysis, ESI-MS, and ¹H NMR. DNA-binding constants of these complexes with calf-thymus DNA (ct-DNA) were determined to be 2.09 (±0.18)?×?10⁴ (mol?L^?1)^?1 (s?=?2.58) and 1.48 (±0.17)?×?10⁵ (mol?L^?1)^?1 (s?=?1.57), respectively. Viscosity measurements show that 1 and 2 interact with ct-DNA by intercalation. Upon irradiation at 365?nm, 1 and 2 induce cleavage of pBR322 DNA. The cytotoxicity of these complexes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis induced by the complexes was studied by flow cytometry. The results of the cell cycle arrest show that 2 can inhibit the proliferation of BEL-7402 cells in the G0/G1 phase.     

Determination of trace amounts of nystatin in water and vaccine samples using sodium dodecyl sulfate-coated iron oxide magnetic nanoparticles followed by high-performance liquid chromatography–ultraviolet detection

In this work, magnetic solid-phase extraction based on sodium dodecyl sulfate-coated Fe₃O₄ nanoparticles has been successfully applied for extraction and preconcentration of trace amounts of nystatin from water and vaccine samples prior to high-performance liquid chromatography–ultraviolet detection. Various experimental parameters affecting extraction and recovery of the analyte, such as the amount of sodium dodecyl sulfate, pH of the sample solution, salt concentration, extraction time, sample volume and desorption conditions, were systematically studied and optimized. Under optimized conditions, nystatin was quantitatively extracted. Proper linear range with good coefficient of determination, (R ² > 0.99) and limit of detection and quantification (based on signal-to-noise ratios of 3 and 10) of 2.0 and 5.0 µg L^?1, over the investigated concentration range (5–700 µg L^?1), were obtained, respectively. The intra-day and inter-day relative standard deviations at 50 µg L^?1 level of NYS were 1.4 and 4.5% based on six replicate determinations. The accuracy of the method was evaluated by recovery measurements on spiked samples. Suitable recoveries of 96–102 and 26–44% were achieved (at spiked levels of 50, 300 and 500 µg L^?1) for water and vaccine samples, respectively.     

Molecular docking,ADME/Tox prediction,and in vitro study of the cell growth inhibitory activity of five β-carboline alkaloids

Structural Chemistry - In a continuing effort to find new cytotoxic, antitumor, and less toxic agents from β-carbolines derivatives, using experimental and computational studies, five...     

Investigation of controlled release properties and anticancer effect of folic acid conjugated magnetic core–shell nanoparticles as a dual responsive drug delivery system on A-549 and A-431 cancer cell lines

Research on Chemical Intermediates - Epirubicin loaded on magnetite-coated calcium ferrite conjugated folic acid (Fe3O4@CaFe2O4-FA@EPI) was synthesized and characterized using various techniques...     

Development of a Henry’s constant correlation and solubility measurements of n-pentane,i-pentane,cyclopentane, n-hexane,and toluene in water

In this communication, we report new experimental data on n-pentane, i-pentane, cyclopentane, n-hexane, and toluene solubility in water at low temperature (below 298.15 K) and atmospheric pressure conditions. The new experimental data together with those reported in the literature have been used in developing a new equation for Henry’s constants of normal alkanes (methane to decane), BETEX compounds, and acid gases in aqueous phase over a wide range of temperature (typically from 273.15 K to 373.15 K). The new equation is based on a thermodynamic model, which uses the Peng–Robinson equation of state combined with the classical quadratic mixing rules for modelling non-aqueous phases, while the NRTL model is used to calculate the water activity.The predictions of the developed thermodynamic model are compared to the experimental data and the results of a thermodynamic approach, which uses the Valderrama modification of the Patel–Teja equation of state and non-density dependent mixing rules for modelling all fluid phases. Good agreement is observed between the experimental data and the model predictions.