Identification, synthesis, and characterization of an unprecedented N-(2-carboxyethyl) adduct impurity in an injectable ganirelix formulation.

Ganirelix, a peptide-based drug used to treat female infertility, has been in high market demand, which attracted generic formulation. A hitherto unknown impurity of ganirelix was observed in our formulation process, which reached ~0.3% in 6 months and led to a detailed investigation of its structure. In-depth analysis of ESI-MS/MS data of this impurity coupled with an artificial intelligence prediction tool led to a highly unusual putative structure, that is, N-(2-carboxyethyl)-ganirelix (NCE-GA), which was authenticated by chemical synthesis from ganirelix and NMR analysis and via corroborated HPLC and MS/MS data with the formulation-derived impurity.

On-resin synthesis of Lanreotide epimers and studies of their structure-activity relationships.

Peptide drugs often accompany epimeric impurities (isomers). Therefore, efficient chemical synthesis of epimers is critical to identify them correctly and investigate their biological activities. Here, we report the rapid synthesis and structure-activity relationship (SAR) studies of eight possible epimers of a somatostatin synthetic analog (SSA), lanreotide (LAN). SPPS and the subsequent on-resin rapid disulfide closure method offered >90% conversion yield for all epimers (P1-P8). Further, we developed an analytical method to separate these epimers, which enabled the profiling of five epimeric impurities in the API, purchased for Somatuline generic formulations. In SAR studies, most LAN epimers revealed compromised antiproliferative activity, while the P7 epimer retained antiproliferative activity similar to LAN API, as supported by in silico SAR studies in detail. Additionally, P7 showed serum stability nearly identical to LAN, suggesting that drug epimers could be a potential API. Current studies will further encourage the development of novel SSA scaffolds.

Green synthesis of silver nanoparticle for catalytic applications and priming study by seed germination.

Silver nanoparticles (AgNPs) have been successfully synthesized using leaf extract of Neem (Azadirachta Indica), Mint (Mentha Piperita), Tulsi (Ocimum Tenuiflorum), Bermuda grass (Cynodon Dactylon) and silver salt. As plant extracts produce best capping material for the stabilization of nanoparticles. AgNPs were characterized by UV-Vis spectroscopy in range of 200-800 nm and transmission electron microscopy TEM, XRD and FTIR. The nanoparticles synthesized were mainly in sizes between 25 and 100 nm. They appeared to be spherical, nanotriangles and irregular in shape. Catalytic application was observed for all the aqueous solution of leaves, quantity taken was 1 ml, 2 ml, 3 ml, 4 ml and 5 ml. Furthermore, prepared Ag nanoparticles are also used for seed germination.

Rapid and Highly Productive Assembly of a Disulfide Bond in Solid-Phase Peptide Macrocyclization.

Here we report a highly efficient disulfide-driven peptide macrocyclization in 15 min on a solid support using persulfate as a crucial additive in iodine-mediated oxidative cyclization. The method eliminates the side products of classical iodine-mediated peptide cyclization. It is operationally simple and convenient for cyclizing small to lengthier peptides embodying popular cysteine building blocks in a single step.

Maximizing EPS production from Pseudomonas aeruginosa and its application in Cr and Ni sequestration.

Heavy metal contamination of water bodies has been a cause of grave concern around the globe. Analysis of various industrial effluents has revealed a perilous level of Cr (VI) and Ni (II). Pseudomonas aeruginosa is an extracellular polymeric substances (EPSs) producing bacterium. EPS has a great potential in the sequestration of heavy metal ions. In the present study efforts have been made to understand the effect of time, pH, and temperature on production of EPS by P. aeruginosa (MTCC 1688). The extracted EPS has been applied for removal of Ni (II) and Cr (VI) ions from aqueous system. The results revealed that highest EPS yield (26 mg/50 mL) can be obtained after 96 h of incubation at pH 6 and 32 °C temperature in 50 mL of culture. Treatment of 10 mg/L Cr (VI) and Ni (II) with 30 mg/L EPS resulted in the removal of 26% and 9% of Cr (VI) and Ni (II), respectively. Fourier-transform infrared spectral analysis revealed the involvement of -OH, -NH, C-O, diketone, and ester functional groups of EPS in the attachment of Cr (VI) ion while involvement of amide and -C[bond, double bond]O groups in Ni (II) binding with EPS. Scaling-up the production of EPS using bioreactor may further help in developing an efficient process for treatment of water polluted with Cr and Ni.

Mechanism of nanotoxicity in Chlorella vulgaris exposed to zinc and iron oxide.

Usage of nanoparticle in various products has increased tremendously in the recent past. Toxicity of these nanoparticles can have a huge impact on aquatic ecosystem. Algae are the ideal organism of the aquatic ecosystem to understand the toxicity impact of nanoparticles. The present study focuses on the toxicity evaluation of zinc oxide (ZnO) and iron oxide (Fe2O3) nanoparticles towards freshwater microalgae, Chlorella vulgaris. The dose dependent growth retardation in Chlorella vulgaris is observed under ZnO and Fe2O3 nanoparticles and nanoform attributed more toxicity than their bulk counterparts. The IC50 values of ZnO and Fe2O3 nanoparticles was reported at 0.258 mg L-1 and 12.99 mg L-1 whereas, for the bulk-form, it was 1.255 mgL-1 and 17.88 mg L-1, respectively. The significant decline in chlorophyll content and increase in proline content, activity of superoxide dismutase and catalase, indicated the stressful physiological state of microalgae. An increased lactate dehydrogenase level in treated samples suggested membrane disintegration by ZnO and Fe2O3 nanoparticles. Compound microscopy, scanning electron microscopy and transmission electron microscopy confirm cell entrapment, deposition of nanoparticles on the cell surface and disintegration of algal cell wall. Higher toxicity of nanoform in comparison to bulk chemistry is a point of concern.

A comparative appraisal of three important oil yielding plants for their biodiesel potential.

In the present scenario, alternative energy sources are required to achieve the future economic prosperity where shortage of fossil fuels will be a limiting factor and hamper the global economic growth. Therefore, interest in biofuel is increasing continuously. The best way of sustainable development is fossil fuel supplementation with biodiesel to reduce the fossil fuel demand. Biodiesel is a clean burning, ester-based, oxygenated fuel derived from natural and renewable sources. Till now, majority of the people have worked on the biodiesel derived from edible oil. Instead of using edible oil, non-edible oil needs to be explored as feedstock for biofuel because half of the world's population is unable to afford the food oil as feedstock for fuel production. Looking at the significance of biodiesel and the resources of biofuel, in this paper, a comparative exhaustive study has been reported with for three important plants, namely Jatropha curcas, Pongemia pinnata and Balanites aegyptiaca. These plants were selected based on their biodiesel potential, availability, cultivation practices and general information available. The present study involves scientometric publications, comparison of fatty acid composition and biodiesel parameters. We have also compared climatic conditions for the growth of the plants, economic feasibility of biodiesel production and other ecological services. The study paves a way for sustainable solution to policy makers and foresters looking for selection of plant species as bioenergy resource.

Recent Developments in Enzymatic Antioxidant Defence Mechanism in Plants with Special Reference to Abiotic Stress.

The stationary life of plants has led to the evolution of a complex gridded antioxidant defence system constituting numerous enzymatic components, playing a crucial role in overcoming various stress conditions. Mainly, these plant enzymes are superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferases (GST), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR), which work as part of the antioxidant defence system. These enzymes together form a complex set of mechanisms to minimise, buffer, and scavenge the reactive oxygen species (ROS) efficiently. The present review is aimed at articulating the current understanding of each of these enzymatic components, with special attention on the role of each enzyme in response to the various environmental, especially abiotic stresses, their molecular characterisation, and reaction mechanisms. The role of the enzymatic defence system for plant health and development, their significance, and cross-talk mechanisms are discussed in detail. Additionally, the application of antioxidant enzymes in developing stress-tolerant transgenic plants are also discussed.

Chromatic intervention and biocompatibility assay for biosurfactant derived from Balanites aegyptiaca (L.) Del.

Extraction of biosurfactants from plants is advantageous than from microbes. The properties and robustness of biosurfactant derived from the mesocarp of Balanites aegyptiaca have been reported. However, the dark brown property of biosurfactant and lack of knowledge of its biocompatibility limits its scope. In the present work, the decolorization protocol for this biosurfactant was optimized using hydrogen peroxide. The hemolytic potential and biocompatibility based on cell toxicity and proliferation were also investigated. This study is the first report on the decolorization and toxicity assay of this biosurfactant. For decolorization of biosurfactant, 34 full factorial design was used, and the data were subjected to ANOVA. Results indicate that 1.5% of hydrogen peroxide can decolorize the biosurfactant most efficiently at 40 °C in 70 min at pH 7. Mitochondrial reductase (MTT) and reactive oxygen species (ROS) assays on M5S mouse skin fibroblast cells revealed that decolorized biosurfactant up to 50 µg/mL for 6 h had no significant toxic effect. Hemolysis assay showed ~ 2.5% hemolysis of human RBCs, indicating the nontoxic effect of this biosurfactant. The present work established a decolorization protocol making the biosurfactant chromatically acceptable. Biocompatibility assays confirm its safer use as observed by experiments on M5S skin fibroblast cells under in vitro conditions.

An appraisal of cuticular wax of Calotropis procera (Ait.) R. Br.: Extraction, chemical composition, biosafety and application.

Plastic and polythene as hydrophobic materials become a grave concern due to their non-biodegradable nature, cumbersome recycling and waste management. Cuticular wax derived from Calotropis procera is explored as an eco-friendly and safe hydrophobic material. The effects of duration of exposure to solvent, solvent type, size and side of the leaf on cuticular wax yield have been studied. Leaf with the smallest area (10 cm2-25 cm2) was found to be the most suitable to isolate the wax. GC-MS analysis of the wax revealed that the wax consists of mainly esters, alkane and alkene. Mitochondrial reductase (MTT) and lactate dehydrogenase (LDH) assay have been carried out on M5S cell line at various concentrations and the results indicate that up to 1 µg/ml (acetone as solvent) and 3 µg/ml (chloroform as solvent) use of wax has no toxic effect. To evaluate the hydrophobic potential of the wax in developing hydrophobic paper water regains and contact angle has been measured. The gain in hydrophobicity of the paper is evident from the rise in contact angle (≥90˚) of paper coated with wax. Scanning electron micrograph and FTIR spectra generated physical and chemical evidence of coating of wax on paper.

Optimization of Extracellular Polymeric Substances production using Azotobacter beijreinckii and Bacillus subtilis and its application in chromium (VI) removal.

Extracellular Polymeric Substances (EPS) of microbial origin are complex biopolymers and vary greatly in their chemical composition. They have a great potential in chelation of metal ions. In this work, the effect of growth phase, temperature and pH on production of EPS by two bacteria Azotobacter beijreinckii and Bacillus subtilis have been studied. Extracted EPS was used to remove Cr(VI) from aqueous system. A. beijreinckii produced maximum EPS after 24h at pH 7 and temperature 30°C while B. subtilis produced maximum EPS after 96h at pH 7 and temperature 37°C. For an initial concentration of 10ppm, 26% and 48% Cr(VI) removal was recorded for EPS derived from A. beijreinckii and B. subtilis respectively. The presence of functional groups on EPS and their interaction with Cr(VI) was confirmed using Fourier-transform infrared (FTIR) spectra analysis. In both the bacteria, carboxyl and phosphate groups show involvement in metal binding.