A New Dimeric Secoiridoid Glycoside from the Leaves of Olea ferruginea Royle

A new dimeric secoiridoid glycoside, trivially named oleferrugine B ( 1 ), has been isolated from the AcOEt‐soluble part of the MeOH extract of leaves of Olea ferruginea Royle . The structure of the isolated compound was established on the basis of ESI‐MS fragmentation patterns, and 1D‐ and 2D‐NMR techniques, including ¹H‐ and ¹³C‐NMR, HSQC, ¹H,¹H‐COSY, HMBC, and NOESY experiments, and by comparison with literature data.     

Biological evaluation of redox stable cisplatin/Cu(II)-DNA adducts as potential anticancer agents

A series of non-enolizable β-diketonate-based copper(II) complexes with LCuCl₂ [L = Knoevenagel condensates of curcumin (Salcimine) and methylacetoacetate (SalMaA)-based Schiff bases] chromospheres as functional models of chemotherapy drug cisplatin were investigated for their covalent interaction with herring sperm DNA. The synthesis and structural characterization of 1a and 1b have been reported in our previous article. However, their DNA interactions and cytotoxicity properties were not studied. These analyses have been carried out mainly through electrochemical techniques supplemented with spectral, relative viscosity, gel electrophoresis techniques, and AGS cancer cells using MTT assay. The cytotoxic activities of the ligand, curcumin-based copper complex, and cisplatin were tested against the AGS cancer cell line under similar experimental conditions showing that the complex exhibited cancer cell inhibitory rate closer to cisplatin even at low concentration. This was also seen in the docking of the Cu-complex onto a rich guanine B-DNA decamer, where a Cu–N3_(guanine) interaction instead of Pt-N7 as cisplatin is detected. The obtained results in this study prove that these complexes could be a promising substitute for cisplatin as a new family of non-platinum-based anticancer metallo-drugs after in vivo tests on animal models.     

Electrochemical studies and potential anticancer activity in ferrocene derivatives

Several ferrocene derivatives (five mononuclear and two binuclear), including the new N-(p-chlorophenyl)-carboxamidoferrocene (1), were synthesized and their anticancer activity investigated. Two of them, 3 and 7, bearing a benzimidazole backbone were the most active against HeLa cells achieving IC₅₀ values of ~5 μM along with 4 with a dipyridylamine ligand (~6 μM). Complex 6, also with a benzimidazole backbone, displayed slightly higher values (~11 μM). Cyclic voltammetry studies show that while the non-cytotoxic ferrocene derivatives 1, 2, and 5 follow a ferrocene-based redox behavior, derivatives 3, 4, 6, and 7 exhibit a more complex mechanism. These complex mechanisms are consistent with a more effective cytotoxic activity. Mössbauer spectroscopy parameters reflect a very small influence of the substituents.     

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts

Polygonum cognatum Meisn. (Polygonaceae) is used both as food and as a folk medicine to treat diabetes. This study aimed to evaluate the effect of the extracts, along with isolated compounds, from P. cognatum aerial parts on diabetes. In vitro studies were conducted using an α-glucosidase inhibitory assay, while in vivo antidiabetic studies were carried out on streptozotocin-induced diabetic rats. Effective extracts were subjected to isolation studies, and structures of the compounds were elucidated by spectroscopic methods. The ethyl acetate and n-butanol extracts had the highest effect in both in vitro and in vivo experiments. They also decreased aspartate transaminase, alanine transaminase and malondialdehyde levels, while increasing glutathione and superoxide dismutase activity in rats. From the active extracts, 11 phenolic compounds were isolated and characterized. Among the isolated compounds, quercetin was found to be the most active according to α-glucosidase inhibitory activity studies. This study provided scientific evidence for the traditional use of P. cognatum as a folk medicine for treating diabetes. The findings suggest that the ethyl acetate and n-butanol extracts, as well as quercetin, have the potential for development as antidiabetic agents.     

Efficient method for screening and identification of radical scavengers in the leaves of Olea europaea L

In this article, an efficient method was developed to screen, isolate and identify the major radical scavengers in the leaves of Olea europaea L. by DPPH‐HPLC‐DAD, HSCCC and NMR. The method of DPPH‐HPLC‐DAD was used to screen the major radical scavengers. It was found that three major constituents (A, B, C) in the extract of the leaves of O. europaea L. possessed potential antioxidant activities. In order to identify the chemical structures of those compounds, the HSCCC method with a two‐phase solvent system composed of petroleum ether–ethyl acetate–water at an optimized volume ratio of 6:600:700 (v/v/v) together with column chromatography was developed to isolate and purify the active compounds. Pure compounds A (225 mg), B (10 mg) and C (12 mg) with purities 92.6, 95.1 and 96.4%, respectively, were obtained from the crude sample (500 mg). Their structures were identified as oleuropein (A), luteolin‐7‐O‐glucoside (B) and verbascoside (C) by ¹H‐NMR and ¹³C‐NMR. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and biological evaluation of new pyrazolebenzene-sulphonamides as potential anticancer agents and hCA I and II inhibitors

Cancer is a disease characterized by the continuous growth of cells without adherence to the rules that healthy normal cells obey. Carbonic anhydrase I and II (CA I and CA II) inhibitors are used for the treatment of some diseases. The available drugs in the market have limitations or side effects, which bring about the need to develop new drug candidate compound(s) to overcome the problems at issue. In this study, new pyrazole-sulphonamide hybrid compounds 4-[5-(1,3-benzodioxol-5-yl)-3-aryl-4,5-dihydro-1 H -pyrazol-1-yl]benzenesulphonamides (4a - 4j) were designed to discover new drug candidate compounds. The compounds 4a - 4j were synthesized and their chemical structures were confirmed using spectral techniques. The hypothesis tested was whether an introduction of methoxy and polymethoxy group(s) lead to an increased potency selectivity expression (PSE) value of the compound, which reflects cytotoxicity and selectivity of the compounds. The cytotoxicity of the compounds towards tumor cell lines were in the range of 6.7 – 400 µM. The compounds 4i (PSE₂ = 461.5) and 4g (PSE₁ = 193.2) had the highest PSE values in cytotoxicity assays. Ki values of the compounds were in the range of 59.8 ± 3.0 - 12.7 ± 1.7 nM towards hCA I and in the range of 24.1 ± 7.1 - 6.9 ± 1.5 nM towards hCA II. While the compounds 4b, 4f, 4g, and 4i showed promising cytotoxic effects, the compounds 4c and 4g had the inhibitory potency towards hCA I and hCA II, respectively. These compounds can be considered as lead compounds for further research.     

Investigation of in vitro cytotoxic,mutagenic and anti-mutagenic effects of shirazolide extracted from Jurinea leptoloba

Shirazolide is an elemanolide isolated from Jurinea leptoloba DC. The aim of this study was to determine the cytotoxic, mutagenic and anti-mutagenic properties of shirazolide from J. leptoloba DC in vitro. Cytotoxicity was measured using a modified MTT (3-(4,5-di methyl thiazol-2-yl)-2,5-di phenyltetrazolium bromide) assay on normal human lymphocytes and tumor HeLa cells, showing that the cytotoxicity of shirazolide is much higher for HeLa cells than for normal lymphocytes. Mutagenic and anti-mutagenic activities of shirazolide were evaluated using the Salmonella typhimurium tester strains TA98 and TA100 showing anti-mutagenic properties against the former strain under metabolic activation.     

Combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells via PI3K/Akt and ERK pathways

The objective of this study was to examine the in vitro combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells FTC133 using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. The present results demonstrated that curcumin at 15–25 μM dose-dependently suppressed the proliferation of FTC133. Combined treatment (curcumin (25 μM) and sorafenib (2 μM)) resulted in a reduction in cell colony formation and significantly decreased the invasion and migration of FTC133 cells compared with that treated with individual drugs. Western blot showed that the levels of p-ERK and p-Akt proteins were significantly reduced (p < 0.01) in the medicine-treated FTC133 cells. The curcumin was found to dose-dependently inhibit the apoptosis of FTC133 cells possibly via PI3K/Akt and ERK pathways. There is a synergetic antitumour effect between curcumin and sorafenib.     

Effect of solvent coordination on the structure of β‐diketone‐based vanadyl complexes and assessment of in vitro antidiabetic activity and cytotoxicity

The physicochemical properties, thereby the biological efficacy, of metal complexes are affected based on their structure and geometry that vary in the presence of coordinating and non‐coordinating solvents. To investigate this, in the present work, we synthesized three hitherto unreported β‐diketone‐based oxovanadium(IV) complexes, namely [VO(tfdmh)₂] (tfdmh =1,1,1‐trifluro‐5,5‐dimethyl‐2,4‐hexanedione), [VO(dmh)₂] (dmh = 2,2‐dimethyl‐3,5‐hexanedione) and [VO(dbm)₂] (dbm = 1,3‐diphenylpropane‐1,3‐dione), and characterized them using electron paramagnetic resonance, UV–visible, Fourier transform infrared and electrospray ionization mass spectroscopies and single‐crystal X‐ray diffraction. The structural changes in the presence of dichloromethane, dimethylsulfoxide and dimethylformamide were analysed using spectroscopic techniques. Further, in vitro glucose uptake efficacy and cytotoxicity were assessed using C2C12 (rat skeletal muscle) and HeLa (human cervical cancer) cell lines, respectively.     

Development and validation of an HPLC-PDA method for the determination of myrsinoic acid B in the extracts of Rapanea ferruginea Mez

New, simple, rapid and precise HPLC-PDA method has been developed and validated for quantification of biomarker myrsinoic acid B in stem bark extracts of Rapanea ferruginea Mez. The method employs a Phenomenex C18 column (250 mm × 4.6 mm I.D., 5 μm) with acetonitrile:methanol:water (pH 2.6 with phosphoric acid) at 48:30:22 as mobile phase, at a flow rate of 0.7 mL min⁻¹ and photo diode array (PDA) detection at 270 nm. The validation data show that the method is specific, accurate, precise and robust. The method was linear, over a range of 5-100.0 μg mL⁻¹, with a limit of detection of 0.369 μg mL⁻¹ and limit of quantification of 1.233 μg mL⁻¹. The method has also shown consistent recoveries (average of 101.3% and 0.12% RSD) of the biomarker, with low intra and inter-day relative standard deviation (1.26% and 1.62%, respectively). The evaluated hydroethanolic extract and dry extract presented MAB values of 63.53 and 36.07 mg g⁻¹, respectively.     

Electrochemical behaviour of a Cu/CuSe microelectrode and its application in detecting temporal and spatial localisation of copper(II) fluxes along Olea europaea roots

The electrochemical behaviour of a Cu/CuSe electrode was studied in order to define its selectivity towards cupric ions, Nerstian response, limit of detection and response time. The chalcogenide electrode was prepared by cathodic deposition of Se and subsequent formation of a thin layer of CuSe on a copper substrate. A Cu/CuSe microelectrode was prepared using copper wire 75 μm in diameter. The dimensions and response time (<0.5 s) allowed use of this electrode in the “vibrating probe method” with the aim of measuring net influxes as well as effluxes of copper(II) ions in Olea europaea roots. The electrode potential was measured along the root at a distance of 5 μm from the surface for 5 s, and then again for 5 s at a distance of 55 μm, moving the microelectrode with respect to the root surface by steps with a frequency of 0.1 Hz. The potentials measured at the two extremes of vibration were then converted to copper(II) concentrations. Substitution of these values in Fick's law yields the flux, assuming the diffusion constant D for copper ions in aqueous solutions. The results enabled us to detect copper(II) fluxes as small as 0.05 pmol cm⁻² s⁻¹. Copper(II) influx showed marked spatial and temporal features: it was highest at about 1.5 mm from the root apex and exhibited an oscillatory pattern in time. Received: 29 September 1999 / Accepted: 11 January 2000     

Screening of Rubiaceae and Apocynaceae extracts for mosquito larvicidal potential

Rubiaceae and Apocynaceae families are well known for the expression of cyclotides having insecticidal properties. Leaves and flowers extracts of plants from the families Rubiaceae (Ixora coccinea) and Apocynaceae (Allamanda violacea) were evaluated for mosquito larvicidal effect against early IVth instars of Aedes aegypti and Anopheles stephensi. Two forms of plant extracts, one untreated and the other treated with heat and proteolytic enzyme were used for assay. After primary assay, the extract showing more than 50% inhibition was further used for quantification purpose. LC₅₀ and LC₉₀ values of all the extracts were found to be reduced with the treated form. Phytochemical analysis of plant extracts was performed. Primary confirmation for the presence of cyclotides was done by Lowry test, thin layer chromatography and haemolytic assay. This novel approach merits use of plant extracts in mosquito control programmes.     

Eco-friendly synthesis of gold nanoparticles using fruit extracts and in vitro anticancer studies

Gold nanoparticles are biocompatible and are having several applications in biomedical Sciences and Engineering. Integration of nanoscience in medicine leads to the development of biomedical products that helps the Society in a faster and safer manner. In the present research work, bioreduction and biofunctionalization of gold nanoparticles are performed with fruit extracts of Aegle marmelos, Eugenia jambolana and soursop. The nanoparticles are characterized using UV–Vis spectroscopy, Transmission Electron Microscopy, Fourier Transform Infrared Spectroscopy and Zeta potentiometer. The qualitative phytochemical analysis of the fruit extracts shows the presence of alkaloids, amino acid, flavonoids, phenol, proteins, tannin, reducing sugars and total Sugars. The in vitro anticancer activity was confirmed by MTT assay on the human breast cancer cell line MCF-7 at different concentrations. The flavonoids present in the fruit extracts are potential reducing agent which is responsible for the formation of gold nanoparticles. Stabilization of gold nanoparticles are performed by the carboxylate group present in the proteins. Also, the nanoparticles are held apart from each other by the electrostatic repulsions that exist due to the presence of like charges surrounding the gold nanoparticles. This study proves that the fruit extracts can be used for the synthesis and stabilization of gold nanoparticles. Further, the engineered nanoparticles capped with bioactive compounds are potential anticancer agents against breast cancer cell line MCF-7.     

Preparation and characterization of microwave-treated carboxymethyl chitin and carboxymethyl chitosan films for potential use in wound care application

CM-chitin and CM-chitosan films were successfully crosslinked by microwave treatment. Crosslinking of the microwave-treated CM-chitin films involved mainly the carboxylate and the secondary alcohol groups, while crosslinking of microwave-treated CM-chitosan films involved the carboxylate and the amino groups. In addition, the crystallinity of CM-chitin increased with increasing microwave treatment time, whereas an increase in the crystallinity of the microwave-treated CM-chitosan films was not observed. At a similar percentage of weight loss, the crosslinking of either CM-chitin or CM-chitosan films by microwave treatment required much less stringent condition when compared with the crosslinking by autoclave treatment. Based on both direct and indirect cytotoxicity assays, the cytotoxicity of the microwave-treated CM-chitin films was negative, while that of the microwave-treated CM-chitosan films was positive. Human fibroblasts adhered on the surface of microwave-treated CM-chitosan films much better than on the surface of microwave-treated CM-chitin films.     

Characterization of extracts from Papaver rhoeas and potential valorization of these extracts in dyeing applications

The aim of our work is to study the dyeing properties of extracts from natural sources such as Papaver rhoeas by modifying the conditions of the dyeing process, choosing other substrates that could be pretreated by innovative and environmentally friendly processes. The results obtained show a fairly high fixation of the extracts on the natural and artificial fibers. The use of mordants allowed the dye to be better fixed on the dyed fibers and to give several shades to the fabric. The rate of essential oil contained in Papaver rhoeas was considered important by the Clevenger process. Screening of extractive revealed the presence of polyphenols, saponins, sterols, alkaloids and flavonoids. In this study, the extractive from Papaver rhoeas was investigated as textile dyestuff.     

Synthesis of 2-aminobenzophenone-based Schiff base Pd(II) complexes: Investigation on crystal structure,biological behavior of DNA/protein-binding,molecular docking,and in vitro anticancer activities

Two new monobasic bidentate ligands and their Pd(II) complexes have been synthesized and characterized by analytical and spectroscopic methods. The structures of the complexes were confirmed by single-crystal X-ray diffraction. The bimolecular binding of the ligands and complexes has been carried out and described. Interestingly, both the bidentate chelating ligands replaced all the triphenyl arsine and chloride ions from the metal precursor in the formation of new complexes and were found to be approximately square planar. The interaction of the ligands and the complexes with calf thymus DNA and bovine serum albumin was studied by electronic and emission spectroscopy techniques, which suggested an intercalation mode of binding. It is well-known that the viscosity of a DNA solution increases if any compound added binds to it through intercalation because this process lengthens the DNA helix due to the increased separation of the DNA base pairs when the compound slides in between, whereas a partial, nonclassical intercalation could bend (or kink) the DNA helix, which leads to a reduction in length and thereby reducing its viscosity. By contrast, there will be no change in the viscosity when the compounds bind with DNA grooves or by partial intercalation, which was further confirmed by viscosity measurements and molecular docking studies. It has been found that the compounds cleaved supercoiled DNA into nicked DNA without any external agent. The in vitro cytotoxicity studies of the ligands and complexes against human lung (A549) and breast (MCF7) cancer cell lines showed significant activity for both species.     

Screening of medicinal plants traditionally used in Peruvian Amazon for in vitro antioxidant and anticancer potential

Plants mentioned in this study have numerous records in traditional Peruvian medicine being used in treatment of cancer and other diseases likely to be associated with oxidative stress. Amongst the eight plant species tested, only Dysphania ambrosioides exhibited combinatory antioxidant and anti-proliferative effect on a broad spectrum of cancer cells (DPPH and ORAC values = 80.6 and 687.3 μg TE/mg extract, respectively; IC₅₀ against Caco-2, HT-29 and Hep-G2 = 129.2, 69.9 and 130.6, respectively). Alkaloids and phenolic compounds might significantly contribute to anticancer/antioxidant activity of this plant. The results justify the traditional medicinal use of this plant. Our findings further suggest that D. ambrosioides might serve as a prospective material for further development of novel plant-based antioxidant and/or anti-proliferative agents. Detailed analysis of chemical composition together with toxicology assessments and in vivo antioxidant/anti-proliferative activity of this plant should be carried out in order to verify its potential practical use.     

Eco-friendly synthesis of ZnO nanorods using Cycas pschannae plant extract with excellent photocatalytic,antioxidant, and anticancer nanomedicine for lung cancer treatment

The tunable ZnO nanorods (NRs) are produced due to the phytochemicals present in Cycas pschannae leaves which act as reducing and stabilizing agents. The confirmations of the ZnO NRs were validated using different characterization techniques: X-ray diffraction, Fourier transform infrared spectroscopy, Brunauer, Emmett and Teller (BET), scanning electron microscopy–Energy Dispersive X-Ray Analysis (EDX), UV–visible spectroscopy, Raman spectroscopy, and transmission electron microscopy. The ZnO NRs show unique surface area and low particle size. Photocatalytic activity was measured and found to be 50.75% at low concentrations and 78.33% at high concentrations. The antioxidant activity of the ZnO NRs also showed promising results for their use in free radical scavenging. In vitro toxicity studies using zebrafish embryos was performed to evaluate the toxic nature of it and the obtained result confirmed its non-toxic nature. In addition, ZnO anticancer potential was verified using the A549 lung cancer cell line. Cytotoxic assessments of ZnO NRs were performed via 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and neutral red uptake assays to examine the cell death cycle on the A549 lung cancer cell. Dose-dependent apoptosis and necrosis were confirmed by Lactate dehydrogenase (LDH) assay. It was also confirmed that ZnO NRs induce Reactive oxygen species (ROS) and apoptosis inside cancer (A549) cells via different intrinsic gene expression. Thus, based on this research it is evident that an effective ecofriendly, nontoxic potential anticancer drug can be synthesized using C. pschannae leaf extract.     

Cucurbit[n]urils (n=7, 8) binding of camptothecin and the effects on solubility and reactivity of the anticancer drug

The interaction between cucurbit[n]uril (n = 7, 8)(Q[n]) with two forms namely lactone modality and carboxylate modality of anticancer drug camptothecin (CPT) was studied. The results revealed that the combination of Q[n] with the lactone form of CPT was observed by electronic absorption spectroscopy, fluorescence spectroscopy and ¹H NMR technique in the acid solution (pH 2) and the total stability constants β were also obtained by Job plot with a host:guest ratio of 2:1; while in the phosphate buffer solution (pH 7.4), only Q[8] bound the carboxylate form of CPT in ratio 1:1, but no obvious interaction between Q[7] and the carboxylate form of CPT was observed. The solubility of CPT was enhanced up to about 70 and 8 times at pH 2 due to the formation of interaction complexes with Q[7] and Q[8], respectively, by using phase solubility method. The cytotoxicity tests revealed that compared with the free CPT, the complexes of Q[n] and CPT had the same cytotoxic activity on the human lung cancer cell line A549 and murine macrophage cell line P388D1 and the moderate depressed activity on human leukaemia cell line K562.