Synthesis and Anticancer Evaluation of Disubstituted Benzimidazoles via One-Pot Telescopic Grinding Approach.

Benzimidazole compounds are known for their broad spectrum therapeutic potentials. A small library of benzimidazole derivatives were designed and synthesized via a one-pot telescopic grinding approach. The ability of these molecules as proposed anticancer agents were evaluated by their potential to bind to two important cancer pathway protein targets, human estrogen receptors and cyclin dependant kinases, 3ERT and 5FGK respectively.

Synthetic access to diverse thiazetidines a one-pot microwave assisted telescopic approach and their interaction with biomolecules.

A one-pot microwave assisted telescopic approach is reported for the chemo-selective synthesis of substituted 1,3-thiazetidines using readily available 2-aminopyridines/pyrazines/pyrimidine, substituted isothiocyanates and 1,2-dihalomethanes. The procedure involves thiourea formation from 2-aminopyridines/pyrazines/pyrimidine with the substituted isothiocyanates followed by a base catalysed nucleophilic attack of the CS bond on the 1,2-dihalomethane. Subsequently, a cyclization reaction occurs to yield substituted 1,3-thiazetidines.

An in silico approach to investigate the theranostic potential of coumarin-derived self-immolative luminescent probes.

Till date the challenge exists in the treatments of cancer for various reasons. Most importantly, the available diagnostics are expensive with research gap for enhancing the cancer detection sensitivity. Herein, a series of coumarin-derived fluorescent theranostic probes are reported that can serve as potent anticancer agents as well as in the detection of cancer cells.

Recent Advancements of Aptamers in Cancer Therapy.

Aptamers are chemical antibodies possessing the capability of overcoming the limitations posed by conventional antibodies, particularly for diagnostic, therapeutic, and theranostic applications in cancer. The ease of chemical modifications or functionalization, including conjugations with nucleic acids, drug molecules, and nanoparticles, has made these aptamers to gain priorities in research. In this Mini-review, various reports on therapeutics with aptamer-functionalized nanomaterials for controlled or multistep drug release, targeted delivery, stimuli-responsive drug release, are discussed.

Click-derived multifunctional metal complexes for diverse applications.

The Click reaction that involves Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) serves as the most potent and highly dependable tool for the development of many complex architectures. It has paved the way for the synthesis of numerous drug molecules with enhanced synthetic flexibility, reliability, specificity and modularity. It is all about bringing two different molecular entities together to achieve the required molecular properties.

Deep Learning-Based Artificial Intelligence to Investigate Targeted Nanoparticles' Uptake in TNBC Cells.

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer in women. It has the poorest prognosis along with limited therapeutic options. Smart nano-based carriers are emerging as promising approaches in treating TNBC due to their favourable characteristics such as specifically delivering different cargos to cancer cells.

Photophysical evaluation on the electronic properties of synthesized biologically significant pyrido fused imidazo[4,5-c]quinolines.

A single pot microwave assisted method was employed to synthesize a series of novel pyrido fused imidazo[4,5-c]quinolines. The electronic properties of these derivatives were investigated by following their photophysical behaviour under isolated and solvated conditions via computational and experimental approaches. The solvatochromic effect of these derivatives was investigated in the ground and excited singlet states by following the absorption and fluorescence emission and excitation spectra.

2,3-Difunctionalized Benzo[]thiophene Scaffolds Possessing Potent Antiangiogenic Properties.

A new class of 2-anilino-3-cyanobenzo[]thiophenes (2,3-ACBTs) was studied for its antiangiogenic activity for the first time. One of the 2,3-ACBTs inhibited tubulogenesis in a dose-dependent manner without any toxicity. The 2,3-ACBTs significantly reduced neovascularization in both and angiogenic assays without affecting the proliferation of endothelial cells.

Antitumor Effects of Ir(III)-2-Indazole Complexes for Triple Negative Breast Cancer.

In this work, we have synthesized a series of novel C,N-cyclometalated 2-indazole-ruthenium(II) and -iridium(III) complexes with varying substituents (H, CH, isopropyl, and CF) in the R position of the phenyl ring of the 2-indazole chelating ligand. All of the complexes were characterized by H, C, high-resolution mass spectrometry, and elemental analysis. The methyl-substituted 2-indazole-Ir(III) complex was further characterized by single-crystal X-ray analysis.

Hepatoprotective and Antioxidant Capacity of Flower Extracts against Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

The aim of the presented work involves the isolation, characterization, and evaluation of hepatoprotective potential of flower extracts. For this purpose, petroleum ether, chloroform, ethyl acetate, alcohol, and water extracts of flower were screened for the flavonoid and phenolic content and quantified. Various antioxidant activity assays including 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing ability were carried out.

Overview of Pathogenesis, Diagnostics, and Therapeutics of Infectious Diseases: Dengue and Zika.

The emergence of more virulent SARS virus has made scientists look back at other so-called neglected diseases such as dengue, Zika, and chikungunya, etc. Until recently these neglected diseases have not received much attention for their control or elimination from society. Over the past decade several attempts to investigate the pathogenicity, diagnostic, and therapeutic strategies for flavivirus caused diseases have been made.

An Overview on the Therapeutics of Neglected Infectious Diseases-Leishmaniasis and Chagas Diseases.

Neglected tropical diseases (NTDs) as termed by WHO include twenty different infectious diseases that are caused by bacteria, viruses, and parasites. Among these NTDs, Chagas disease and leishmaniasis are reported to cause high mortality in humans and are further associated with the limitations of existing drugs like severe toxicity and drug resistance. The above hitches have rendered researchers to focus on developing alternatives and novel therapeutics for the treatment of these diseases.

Diversity-Oriented Synthesis of Thiazolidine-2-imines via Microwave-Assisted One-Pot, Telescopic Approach and Its Interaction with Biomacromolecules.

In this work, a one-pot, telescopic approach is described for the combinatorial library of thiazolidine-2-imines. The synthetic manipulation proceeds smoothly via the reaction of 2-aminopyridine/pyrazine/pyrimidine with substituted isothiocyanates followed by base catalyzed ring closure with 1,2-dibromoethane to obtain thiazolidine-2-imines with broad substrate scope and high functional group tolerance. The synthetic strategy merges well with the thiourea formation followed by base catalyzed ring closure reaction for the thiazolidine-2-imine synthesis in a more modular and straightforward approach.

Synthesis and Antitumor Activity Evaluation of Cyclometalated 2H-Indazole Ruthenium(II) and Iridium(III) Complexes.

In this work, a series of novel C-N cyclometalated 2H-indazole Ru(II) and Ir(III) complexes were synthesized, wherein chelating ligands with substituents like H, and isopropyl group in the R position of the phenyl ring of the 2H-indazole chelating ligand are present. The cytotoxicity of Ru(II) and Ir(III) complexes has been evaluated against different human cancer cell lines (HeLa, MCF-7, and A549) in a concentration-dependent manner. The new iridium complex with isopropyl substituent in the phenyl ring of the 2H-indazole moiety showed good cytotoxic activity against MCF-7 cells with an IC value 3.

One-Pot, Telescopic Approach for the Chemoselective Synthesis of Substituted Benzo[]pyrido/pyrazino/pyridazino[1,2-][1,2,4]thiadiazine dioxides and Their Significance in Biological Systems †.

The one-pot telescopic approach has been developed for the chemoselective synthesis of substituted benzo[]pyrido/pyrazino/pyridazino[1,2-][1,2,4]thiadiazine dioxides using readily available 2-aminopyridines/pyrazines/pyridazine and 2-chloro benzene sulfonyl chloride. This one-pot procedure involves the chemoselective sulfonylation of 2-aminopyridines/pyrazines/pyridazine with 2-chloro benzene sulfonyl chloride followed by a Cu(I)-catalyzed Ullmann-type C-N coupling reaction to obtain benzo[]pyrido/pyrazino/pyridazino[1,2-][1,2,4]thiadiazine dioxides with broad substrate scope and high functional group tolerance. The synthetic sequence merges well with the nucleophilic attack on the 2-amino group of pyridines/pyrazines/pyridazines on the 2-chloro benzene sulfonyl chloride, followed by Cu(I)-catalyzed ipso chloro displacement to C-N bond formation resulting in a more modular and straightforward approach.

Design, synthesis and identification of novel coumaperine derivatives for inhibition of human 5-LOX: Antioxidant, pseudoperoxidase and docking studies.

5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors especially, natural product based ones, are highly attractive. Coumaperine, a natural product found in white pepper and its derivatives were herein developed as 5-LOX inhibitors.

Decolorization of Distillery Spent Wash Using Biopolymer Synthesized by Pseudomonas aeruginosa Isolated from Tannery Effluent.

A bacterial strain was isolated from tannery effluent which can tolerate high concentrations of potassium dichromate up to 1000 ppm. The isolated microorganism was identified as Pseudomonas aeruginosa by performing biochemical tests and molecular characterization. In the presence of excess of carbohydrate source, which is a physiological stress, this strain produces Polyhydroxybutyrate (PHB).

Enhancing precursors availability in Pichia pastoris for the overproduction of S-adenosyl-L-methionine employing molecular strategies with process tuning.

S-Adenosyl-L-methionine (SAM) is an important metabolite having prominent role in treating various diseases. Due to increasing demand of SAM, improvement in its production is essential. For this purpose, S-adenosyl-l-methionine synthetase gene (sam2) was overexpressed in the present study, and we studied the effect of coexpression of methionine permease (mup1) and adenylate kinase (adk1) genes.

Bacterial lipid modification of proteins requires appropriate secretory signals even for expression - implications for biogenesis and protein engineering.

Sec- and Tat-mediated bacterial lipid modification of proteins are important posttranslational processes owing to their vital roles in cellular functions, membrane targeting and biotechnological applications like ELISA, biosensor, adjuvant-free vaccines, liposomal drug delivery etc. However a better understanding of the tight coupling of secretory and lipid modification machineries and the processes associated will help unravel this essential biological event and utilize it for engineering applications. Further, there is a need for a systematic and convincing investigation into membrane targeting, solubilization and ease-of-purification of engineered lipoproteins to facilitate scientists in readily applying this new protein engineering tool.

An "escape clock" for estimating the turnover of SIV DNA in resting CD4⁺ T cells.

Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection.

Design and characterization of stabilized derivatives of human CD4D12 and CD4D1.

CD4 is present on the surface of T-lymphocytes and is the primary cellular receptor for HIV-1. CD4 consists of a cytoplasmic tail, one transmembrane region, and four extracellular domains, D1-D4. A construct consisting of the first two domains of CD4 (CD4D12) is folded and binds gp120 with similar affinity as soluble 4-domain CD4 (sCD4).

Ligand-modulated parallel mechanical unfolding pathways of maltose-binding proteins.

Protein folding and unfolding are complex phenomena, and it is accepted that multidomain proteins generally follow multiple pathways. Maltose-binding protein (MBP) is a large (a two-domain, 370-amino acid residue) bacterial periplasmic protein involved in maltose uptake. Despite the large size, it has been shown to exhibit an apparent two-state equilibrium unfolding in bulk experiments.

Mitochondrial NADH kinase, Pos5p, is required for efficient iron-sulfur cluster biogenesis in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the mitochondrial inner membrane readily allows transport of cytosolic NAD(+), but not NADPH, to the matrix. Pos5p is the only known NADH kinase in the mitochondrial matrix. The enzyme phosphorylates NADH to NADPH and is the major source of NADPH in the matrix.

Does cytolysis by CD8+ T cells drive immune escape in HIV infection?

CD8(+) "cytotoxic" T cells are important for the immune control of HIV and the closely related simian models SIV and chimeric simian-human immunodeficiency virus (SHIV), although the mechanisms of this control are unclear. One effect of CD8(+) T cell-mediated recognition of virus-infected cells is the rapid selection of escape mutant (EM) virus that is not recognized. To investigate the mechanisms of virus-specific CD8(+) T cell control during immune escape in vivo, we used a real-time PCR assay to study the dynamics of immune escape in early SHIV infection of pigtail macaques.

Designed biomaterials to mimic the mechanical properties of muscles.

The passive elasticity of muscle is largely governed by the I-band part of the giant muscle protein titin, a complex molecular spring composed of a series of individually folded immunoglobulin-like domains as well as largely unstructured unique sequences. These mechanical elements have distinct mechanical properties, and when combined, they provide the desired passive elastic properties of muscle, which are a unique combination of strength, extensibility and resilience. Single-molecule atomic force microscopy (AFM) studies demonstrated that the macroscopic behaviour of titin in intact myofibrils can be reconstituted by combining the mechanical properties of these mechanical elements measured at the single-molecule level.