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Amyloids are associated with many neurodegenerative diseases, motivating investigations into their structure and function. Although not linked to a specific disease, albumins have been reported to form many structural aggregates. We were interested in investigating host immune responses to amyloid fibrils assembled from the model protein ovalbumin. Surprisingly, upon subjecting ovalbumin to standard denaturing conditions, we encountered giant protein nanosheets harboring amyloid-like features and hypothesized that these nanosheets might have potential in clinical or therapeutic applications. We found that the nanosheets, without the administration of any additional adjuvant, evoked a strong antibody response in mice that was higher than that observed for native ovalbumin. This suggests that amyloid nanosheets have a self-adjuvanting property. The nanosheet-induced immune response was helper T cell 2 (Th2) biased and negligibly inflammatory. While testing whether the nanosheets might form depots for the sustained release of precursor proteins, we did observe release of ovalbumin that mimicked the conformation of native protein. Moreover, the nanosheets could load the anticancer drug doxorubicin and release it in a slow and sustained manner. Taken together, our results suggest that amyloid nanosheets should be further investigated as either an antigen delivery vehicle or a multifunctional antigen and drug co-delivery system, with potential applications in simultaneous immunotherapy and chemotherapy.

A series of steroidal oxazole and thiazole derivatives have been synthesized employing thiosemicarbazide/semicarbazide hydrochloride and ethyl 2-chloroacetoacetate with a simple and facile one-pot multicomponent reaction pathway. The antimicrobial activity of newly synthesized compounds were evaluated against four bacterial strains namely Gram-negative (Escherichia coliand Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) in addition to pathogenic fungi (Candida albicans and Cryptococcus neoformans). Bioactivity assay manifested that most of the compounds exhibited good antimicrobial activity. To provide additional insight into antimicrobial activity, the compounds were also tested for their antibiofilm activity against S. aureus biofilm. Moreover, molecular docking study shows binding of compounds with amino acid residues of DNA gyrase and glucosamine-6-phosphate synthase (promising antimicrobial target) through hydrogen bonding interactions. Hemolytic activity have been also investigated to ascertain the effect of compounds over RBC lysis and results indicate good prospects for biocompatibility. The expedient synthesis of steroidal heterocycles, effective antibacterial and antifungal behavior against various clinically relevant human pathogens, promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.

In the present manuscript, a series of steroidal thiazole derivatives (4–6, 8) have been synthesized in efficient manner by one step reaction methodology employing microwave irradiation. The synthesis involves the reaction of steroidal ketones (1–3, 7) with thiosemicarbazide and phenacyl bromide. Structural assignment of the products was confirmed on the basis of IR, 1H NMR, 13C NMR, MS and analytical data. The synthesized compounds were screened for in vitro antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. In addition, the products 4–6, 8 were also tested for pBR322 DNA cleavage activity, genotoxicity, reactive oxygen species (ROS) production and RBC hemolysis. Molecular docking analysis was carried out to validate the specific binding mode of the newly synthesized compounds into the active site of DNA. Docking showed formation of more stable complexes of compounds 4 and 8 with the free binding energies − 8.1 and − 8 kcal/mol, respectively. Hence, it could be suggested that the steroidal compounds bearing a core thiazole scaffold would be a potent biological agent.

The doping of semiconductor by rare earth metals nanoparticles is an effective way for increasing photocatalytic activity. Zinc oxide and Lanthanum doped Zinc oxide nanoparticles were synthesized by modifying the gel-combustion method. It was found that La can greatly enhance the cytotoxicity and photocatalytic activity of ZnO nanoparticles towards various cell lines and Paracetamol drug. These nanoparticles were characterized by various spectroscopic and other techniques which clearly revealed the presence of lanthanum ions. The absorption edge shifts towards the visible region after doping with La ions. This shift shows that the doping of La ions is favorable for absorbing the visible light. The comparative photocatalytic and cytotoxicity activity revealed that La doped ZnO nanoparticles remarkably enhanced activities as compared to the ZnO nanoparticles. The outcome of these studies offers valuable for planning La doped ZnO nanoparticles having cytotoxicity and photocatalytic activities helpful for the formulation of anticancer product and waste water remediation.

The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a–k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a–k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski’s rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. Keywords: Imidazolidine, Indomethacin, Anti-inflammatory, Analgesic

A novel series of metal complexes of the types, [ML 2 (H 2 O) 2 ]Cl 2 and [ML 2 ]Cl 2 [M = Mn(II), 1 ; Co(II), 2 ; Ni(II), 3 ; Cu(II), 4 ; and Zn(II), 5 ] were synthesized by the interaction of ligand, L (E)-N-(furan-2-yl methylene) quinolin-8-amine, derived from the condensation of 2-furaldehyde and 8-aminoquinoline. The synthesized ligand and its metal complexes were characterized on the basis of results obtained from elemental analysis, ESI-MS, XRD, SEM, TGA/DTA, FT-IR, UV-Vis, magnetic moment and 1 H and 13 C NMR spectroscopic studies. EPR parameters were recorded in case of complex 4 . The comparative in-vitro antimicrobial activities against various pathogens with reference to known antibiotics and antioxidant activity against standard control at variable concentrations revealed that the metal complexes show enhanced antimicrobial and free radical scavenging activities in general as compared to free ligand. However, the complexes 1 and 5 have shown best antioxidant activity among all the metal complexes. Furthermore, comparative in-vitro antiproliferative activity on ligand and its metal chelates performed on MDA-MB-231 (breast carcinoma), KCL22 (blood lymphoid carcinoma), HeLa (cervical carcinoma) cell lines and normal cells (PBMC) revealed that metal chelates show moderate to good activity as compared to ligand where as complex 1 seems to be the most promising one possessing a broad spectrum of activity against all the selected cancer cell lines with IC 50

The present work describes a convenient synthesis of steroidal spirothiazolidinone derivatives ( 3 , 10 – 12 ) in a two-step process. All the newly synthesized compounds have been characterized by means of elemental analyses, IR, 1 H NMR, 13 C NMR and MS. Lipinski’s ‘Rule of Five’ analysis and biological score predicted higher intrinsic quality of the synthesized compounds and revealed that these compounds have good passive oral absorption. The DNA binding studies of the synthesized compounds with CT-DNA were carried out by UV–vis and fluorescence spectroscopy. The molecular docking study suggested electrostatic interaction between synthesized compounds and nucleotide base pairs. The antitumor activity was tested in vitro against human leukemia cancer cell (Jurkat) and blood peripheral mononuclear normal cell (PBMCs) lines by MTT method. In addition, apoptosis and nonenzymatic degradation of DNA have been investigated. The acetylcholinesterase (AChE) inhibitor activities of the derivatives were also evaluated using Ellman’s method. The present study has shown that steroidal spirothiazolidinone derivatives ( 3 , 10 – 12 ) can be used as template to design more potent and selective cytotoxic and AChE inhibition agents through modification and derivatization.

Amyloids are highly organized protein aggregates that arise from inappropriately folded versions of proteins or polypeptides under both physiological as well as simulated ambiences. Once thought to be irreversible assemblies, amyloids have begun to expose their more dynamic and reversible attributes depending upon the intrinsic properties of the precursor protein/peptide and experimental conditions such as temperature, pressure, structural modifications in proteins, or presence of chemicals in the reaction mixture. It has been repeatedly proposed that amyloids undergo transformation to the bioactive peptide/protein forms under specific conditions. In the present study, amyloids assembled from the model protein ovalbumin (OVA) were found to release the precursor protein in a slow and steady manner over an extended time period. Interestingly, the released OVA from amyloid depot was found to exhibit biophysical characteristics of native protein and reacted with native-OVA specific monoclonal as well as polyclonal antibodies. Moreover, antibodies generated upon immunization of OVA amyloidal aggregates or fibrils were found to recognize the native form of OVA. The study suggests that amyloids may act as depots for the native form of the protein and therefore can be exploited as vaccine candidates, where slow antigen release over extended time periods is a pre-requisite for the development of desired immune response.

In this study, we describe a green and simple procedure for the synthesis of steroidal 2 H -pyrans 4 – 6 using chitosan as an eco-friendly heterogeneous catalyst. The synthesized compounds were characterized by IR, 1 H NMR, 13 C NMR, MS and analytical data. These compounds were tested in vitro against two cancer cell lines [HeLa (cervical) and Jurkat (leukemia)] and one normal cell line (PBMC). The compounds exhibited moderate to good activity against the two human cancer cell lines and were less toxic against the non-cancer cell line. In addition, the synthesized compounds were tested for their in vitro antioxidant activity by 1,1-diphenylpicrylhydrazyl method in which compounds 4 and 6 exhibited good antioxidant activity. This study provided a new molecular scaffold for the further development of anticancer as well as antioxidant agents.

The term 'agile manufacturing' has referred to operational aspects of a manufacturing company concerning their ability to produce customized products at mass production prices and with short lead times. A core issue faced within agile manufacturing is the need for appropriate and supporting production and operations systems. Many design dimensions of agility and agile manufacturing exist. To help attain this goal for integrating the many design dimensions, operations infrastructure and capacity must be carefully planned to manage production flow, and thus production layout planning takes on an increasingly important role. Given the importance of these dimensions in response to agility, this paper seeks to make a contribution by providing insights into a decision aid for evaluating production flow layouts that support and enhance the agile manufacture of products. Layout design has a significant impact on the performance of a manufacturing or service industry system and has been an active research area for many decades. Strategic evaluation of production layouts requires consideration of both qualitative and quantitative factors (managerial, organizational, and technical). This paper makes use of the Analytical Network Process (ANP) which captures interdependencies among different criteria, sub-criteria and dimensions, an evident characteristic of production flow layouts in complex agile manufacturing environments. An application case study exemplifying the practical usefulness of this type of model describes how management, after implementation of the model, made a mid-course correction related to the production layout initially selected.

Deepak Yadav, Veena Garg, Anis A. Chaudhary, Mohammad F. Anwar, Hemant Kardam, Mohammad N. Beg, Suruchi Suri, Mohd Asif a Drug Standardization Lab, Department of Ilmul-Advia, F/o Medicine, Hamdard University, New Delhi-110062, India Department of Bioscience and Biotechnology, Banasthali University, Rajasthan-304022, India Department of Chemistry, F/o Science, Hamdard University, New Delhi-110062, India Department of Botany, F/o Science, Hamdard University, New Delhi-110062, India Nanomedicine Lab, F/o Pharmacy, Hamdard University, New Delhi-110062, India

Chlorides of a variety of acids: primary, secondary, tertiary, long chain aliphatic and αβ-unsaturated have been converted into aldehydes by reduction with formic acid at pH 9–10 at room temperature in high yields.