Conformation and Cytotoxicity of a Tetrapeptide Constellated with Alternative D- and L-proline

Proline containing peptides are highly important due to their natural abundance in various secondary structural elements like turns (b turn and c turn etc.) in proteins. Here the conformation, cytotoxicity and structure of a unique tetrapeptide composed of alternative D- and L-proline residues are discussed. The peptide showed a polyproline II like conformation in dilute aqueous solution. The aqueous solution of the peptide self-assembled to form spheroidal oligomers with a diameter of y90 nm. The morphological features were confirmed by bright field confocal images, TEM analysis and AFM. The alternative D- and Lproline residues in the peptide showed toxicity towards cancer cell lines and y50% cell death was recorded against three different types of cancer cells (Neura 2a, HEK 293 and Hep G2)

Synthesis, Characterization and Cytotoxicity study of Magnetic (Fe3O4)Nanoparticles and their Drug Conjugate

An easy synthesis of magnetic nanoparticles (Fe3O4) is described. Transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and X-ray diffraction (XRD) have been used to study the well dispersed and uniformly spherical nanoparticles. 5-Fluorouracil (5-FU) has been successfully loaded onto the nanoparticles and cytotoxicity studies were performed using a standard MTT assay. The results indicate that 5-fluorouracil-loaded iron nanoparticles are a more potent anticancer drug versus 5-fluorouracil alon

Energy Conversion Strategies for Wind Energy System: Electrical, Mechanical and Material Aspects

Currently, about 22% of global electricity is being supplemented by different renewable sources. Wind energy is one of the most abundant forms of renewable energy available in the atmospheric environment due to different air-currents spread over the troposphere and stratosphere. The demand of modern wind energy conversion system (WECS) has increased to achieve a suitable alternate renewable energy source. In this paper, after a brief introduction, the classification of WECS is reviewed with attractive illustrations. The various mechanical materials and electrical components of WECS are discussed. The flow of power in WECS and its control strategies are also been described. The wind energy conversion is carried out with a suitable controlling mechanism for power grid integration. A maximum power-point tracking controller is an effective controlling method to extract the maximum possible power from the turbines. The present trends in WECS and the scope for improvement and future prospects are discussed. The materials used for both the blade and generator have been found to be key elements of wind turbines. Recycling of the polymer matrix composite materials are found to be a great threat to wind power plants, as well as to their supply chain industries

Efficacy of cyclin dependent kinase 4 inhibitors as potent neuroprotective agents against insults relevant to Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no cure till today. Aberrant activation of cell cycle regulatory proteins is implicated in neurodegenerative diseases including AD. We and others have shown that Cyclin dependent kinase 4 (Cdk4) is activated in AD brain and is required for neuron death. In this study, we tested the efficiency of commercially available Cdk4 specific inhibitors as well as a small library of synthetic molecule inhibitors targeting Cdk4 as neuroprotective agents in cellular models of neuron death. We found that several of these inhibitors significantly protected neuronal cells against death induced by nerve growth factor (NGF) deprivation and oligomeric beta amyloid (Aβ) that are implicated in AD. These neuroprotective agents inhibit specifically Cdk4 kinase activity, loss of mitochondrial integrity, induction of pro-apoptotic protein Bim and caspase3 activation in response to NGF deprivation. The efficacies of commercial and synthesized inhibitors are comparable. The synthesized molecules are either phenanthrene based or naphthalene based and they are synthesized by using Pschorr reaction and Buchwald coupling respectively as one of the key steps. A number of molecules of both kinds block neurodegeneration effectively. Therefore, we propose that Cdk4 inhibition would be a therapeutic choice for ameliorating neurodegeneration in AD and these synthetic Cdk4 inhibitors could lead to development of effective drugs for AD

Small-Molecule Cdc25A Inhibitors Protect Neuronal Cells from Death Evoked by NGF Deprivation and 6‑Hydroxydopamine

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases that are presently incurable. There have been reports of aberrant activation of cell cycle pathways in neurodegenerative diseases. Previously, we have found that Cdc25A is activated in models of neurodegenerative diseases, including AD and PD. In the present study, we have synthesized a small library of molecules targeting Cdc25A and tested their neuroprotective potential in cellular models of neurodegeneration. The Buchwald reaction and amide coupling were crucial steps in synthesizing the Cdc25A-targeting molecules. Several of these small-molecule inhibitors significantly prevented neuronal cell death induced by nerve growth factor (NGF) deprivation as well as 6-hydroxydopamine (6-OHDA) treatment. Lack of NGF signaling leads to neuron death during development and has been associated with AD pathogenesis. The NGF receptor TrkA has been reported to be downregulated at the early stages of AD, and its reduction is linked to cognitive failure. 6-OHDA, a PD mimic, is a highly oxidizable dopamine analogue that can be taken up by the dopamine transporters in catecholaminergic neurons and can induce cell death by reactive oxygen species (ROS) generation. Some of our newly synthesized molecules inhibit Cdc25A phosphatase activity, block loss of mitochondrial activity, and inhibit caspase-3 activation caused by NGF deprivation and 6-OHDA. Hence, it may be proposed that Cdc25A inhibition could be a therapeutic possibility for neurodegenerative diseases and these Cdc25A inhibitors could be effective treatments for AD and PD

Aggregation-Induced Emission of Contorted Polycondensed Aromatic Hydrocarbons Made by Edge Extension Using a Palladium-Catalyzed Cyclopentannulation Reaction

Contorted polycyclic aromatic hydrocarbons (PAHs), CPA1–2 and CPB1–2, bearing peripheral five-membered rings were synthesized employing a palladium-catalyzed cyclopentannulation reaction using specially designed diaryl acetylene synthons TPE and TPEN with commercially available dibromo- anthracene DBA and bianthracene DBBA derivatives. The resulting target compounds CPA1–2 and CPB1–2 were isolated in excellent yield and found to be highly soluble in common organic solvents, which allowed for their structural characterization and investigation of the photophysical properties, disclosing their aggregation-induced emission (AIE) properties in THF at selective concentration ranges of water fractions in the solvent mixture. Examination of the contorted PAH structures by means of density functional theory (DFT) revealed higher electronic conjugation in the more rigid and planar anthracene-containing CPA1–2 derivatives when compared to the twisted bianthracene-bearing moieties CBPA1–2 with HOMO–LUMO bandgaps (ΔE) of ∼2.32 eV for the former PAHs and ∼2.78 eV for the latter ones

Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy

Controlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm−2) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH3)2) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence of BODIPY(PPH3)2. This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer

Ultrasensitive Reagent for Ratiometric Detection and Detoxification of iAsIII in Water and Mitochondria

Toxicity induced by inorganic arsenic as AsO33– (iAsIII) is of global concern. Reliable detection of the maximum allowed contaminant level for arsenic in drinking water and in the cellular system remains a challenge for the water quality management and assessment of toxicity in the cellular milieu, respectively. A new Ir(III)-based phosphorescent molecule (AS-1; λExt = 415 nm and λEms = 600 nm, Φ = 0.3) is synthesized for the selective detection of iAsIII in an aqueous solution with a ratiometric luminescence response even in the presence of iAsV and all other common inorganic cations and anions. The relatively higher affinity of the thioimidazole ligand (HPBT) toward iAsIII led to the formation of a fluorescent molecule iAsV–HPBT (λExt = 415 nm and λEms = 466 nm, Φ = 0.28) for the reaction of iAsIII and AS-1. An improved limit of quantitation (LOQ) down to 0.2 ppb is achieved when AS-1 is used in the CTAB micellar system. Presumably, the cationic surfactants favor the localization of AS-1@CTABMicelle in mitochondria of MCF7 cells, and this is confirmed from the images of the confocal laser fluorescence scanning microscopic studies. Importantly, cell viability assay studies confirm that AS-1@CTABMicelle induces dose-dependent detoxification of iAsIII in live cells. Further, luminescence responses at 466 nm could be utilized for developing a hand-held device for the in-field application. Such a reagent that allows for ratiometric detection of iAsIII with LOQ of 2.6 nM (0.5 ppb) in water, as well as helps in visualizing its distribution in mitochondria with a detoxifying effect, is rather unique in contemporary literature

Process for Preparing Value-Added Products from Microalgae Using Textile Effluent through a Biorefinery Approach

A model was designed for effective utilization of textile effluent as the nutrient medium for the production of high-value products from Chlorella variabilis through a greener approach. Biomass productivity of 74.96 ± 2.62 g/(m²/d) with lipid yield of 20.1 ± 2.2% (wrt dry biomass) was obtained using textile effluent as the nutrient source. A novel integrated process is developed based on detergent (sodium dodecyl sulfate) hydrolysis to convert the carbohydrates present in microalgal biomass to reducing sugars for microbial fermentation, while making available lipids for downstream processing of γ-linolenic acid, leaving the protein rich fragment behind. Our experimental data showed that from 495 g of microalgal biomass, 109.4 g total lipids was extracted containing 34.65 g γ-linolenic acid, and 1.3 g pure ε-polylysine from 36.68 g of reducing sugars. A two-step efficient green process was developed for recovering ε-polylysine using ethyl­ammonium nitrate having 74% recovery. In addition to value-added products, CSIR-CSMCRI’s Chlorella variabilis (ATCC PTA 12198) can remediate 100% of aluminum, 82.72% boron, 45.66% calcium, 100% cobalt, 14.5% potassium, 0.1% magnesium, 42.18% sodium, 100% nickel, and 100% iron. A total decrease of 78.17% total phosphate and 25.22% total inorganic phosphate with respect to total phosphate present in the effluent was observed