Recent Developments in the Use of Kinase Inhibitors for Management of Viral Infections.

Kinases are a group of therapeutic targets involved in the progression of numerous diseases, including cancer, rheumatoid arthritis, Alzheimer's disease, and viral infections. The majority of approved antiviral agents are inhibitors of virus-specific targets that are encoded by individual viruses. These inhibitors are narrow-spectrum agents that can cause resistance development.

Dihydropyrimidinones: efficient one-pot green synthesis using Montmorillonite-KSF and evaluation of their cytotoxic activity.

A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by "HPA-Montmorillonite-KSF" as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions.

Determination of bioactive compounds of Artemisia Spp. plant extracts by LC-MS/MS technique and their in-vitro anti-adipogenic activity screening.

Ultra Performance Liquid Chromatography coupled with hybrid triple quadrupole linear ion trap tandem mass spectrometry (UPLC-ESI-QqQ-MS/MS) method in multiple reaction monitoring (MRM) acquisition mode was developed and validated for identification and simultaneous determination of potential anti-diabetic and anti-malarial compounds in ethanolic extracts of different Artemisia species. The chromatographic separation was carried out on an Acquity BEH™ C column (1.7 μm, 2.

Dimethoate Induces DNA Damage and Mitochondrial Dysfunction Triggering Apoptosis in Rat Bone-Marrow and Peripheral Blood Cells.

Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats.

Discovery of a New Donepezil-like Acetylcholinesterase Inhibitor for Targeting Alzheimer's Disease: Computational Studies with Biological Validation.

Alzheimer's disorder is one of the most common worldwide health problems, and its prevalence continues to increase, thereby straining the healthcare budgets of both developed and developing countries. So far, donepezil is the only Food and Drug Administration-approved dual-binding site inhibitor of acetylcholinesterase (AChE) that can amplify the cholinergic activity and also decrease Aβ aggregation in Alzheimer patients. We report herein a new donepezil-like natural compound derivative (D1) as a convincing AChE inhibitor.

Discovery of methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide as a blood-brain permeable dual inhibitor of acetylcholinesterase and butyrylcholinesterase.

The cholinesterase enzymes play a vital role in maintaining balanced levels of the neurotransmitter acetylcholine in the central nervous system. However, the overexpression of these enzymes results in hampered neurotransmission. Both the major forms of cholinesterase enzymes viz.

Chiral Transient Directing Group Strategies in Asymmetric Synthesis.

The development of novel methodologies for catalytic enantioselective functionalization reactions enabled by chiral transient directing groups is accompanying in a paradigm shift in the field of asymmetric synthesis. In particular, these highly atom- and step-economic enantioinduction processes commonly proceed either via enantioselective C-H functionalization, or via enantioselective hydroarylation of the pro-chiral substrates generating point, axial or planar chirality. The use of the transient directing group strategy in C-H functionalizations precludes the stoichiometric installations and removal of directing groups and enables efficient, more compatible and economical chemical routes.

Recent advances in tumor microenvironment associated therapeutic strategies and evaluation models.

As per a report of the world health organization, an estimated 9.6 million people died due to cancer in 2018, globally. Most of the cancer death attributed to the lack of early detection and effective treatment.

Recent Advances in Strategies for Extracellular Matrix Degradation and Synthesis Inhibition for Improved Therapy of Solid Tumors.

Despite a great deal of efforts made by researchers and the advances in the technology, the treatment of cancer is very challenging. Significant advances in the field of cancer therapeutics have been made but due to the complexity of solid tumor microenvironment, specially their dense extracellular matrix (which makes the conditions favorable for cancer growth, metastasis and acts as a barrier to the chemotherapeutic drugs as well as nanomedicine), the treatment of solid tumors is difficult. Overexpression of extracellular matrix components such as collagen, hyaluronan and proteoglycans in solid tumor leads to high interstitial fluid pressure, hypoxia, vascular collapse and poor perfusion which hinder the diffusion and convection of the drugs into the tumor tissue.

Drug resistance in cancer: mechanisms and tackling strategies.

Drug resistance developed towards conventional therapy is one of the important reasons for chemotherapy failure in cancer. The various underlying mechanism for drug resistance development in tumor includes tumor heterogeneity, some cellular levels changes, genetic factors, and others novel mechanisms which have been highlighted in the past few years. In the present scenario, researchers have to focus on these novel mechanisms and their tackling strategies.

Advances in the possible treatment of COVID-19: A review.

The emergence of the global pandemic caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put a challenge to identify or derive the therapeutics for its prevention and treatment. Despite the unprecedented advances in the modern medicinal system, currently, there are no proven effective therapies. However, rapid research on SARS-CoV-2 epidemiology help unveiling some new targets for potential drug therapies.

Total Synthesis of Phospholipomannan of .

First, total synthesis of the cell surface phospholipomannan anchor [β-Man-(1 → 2)-β-Man]-(1 → 2)-β-Man-(1 → 2)-α-Man-1 → -( → 6)-α-Man-(1 → 2)-Inositol-1--( → 1)-phytoceramide of is reported. The target phospholipomannan (PLM) anchor poses synthetic challenges such as the unusual kinetically controlled (1 → 2)-β-oligomannan domain, anomeric phosphodiester, and unique phytoceramide lipid tail linked to the glycan through a phosphate group. The synthesis of PLM anchor was accomplished using a convergent block synthetic approach using three main appropriately protected building blocks: (1 → 2)-β-tetramannan repeats, pseudodisaccharide, and phytoceramide-1--phosphonate.

Evaluation of rohitukine-enriched fraction of Dysoxylum binectariferum Hook.f. (leaves) as anti-arthritic phytopharmaceutical candidate: Chemical standardization, in-vivo validation, formulation development and oral pharmacokinetics.

Ethnopharmacological Relevance: Rheumatoid arthritis is a chronic inflammatory disease of joints. Dysoxylum binectariferum Hook.f (Family: Meliaceae) is a Indian medicinal plant which is traditionally being used to heal inflammation of joints.

Oxone-DMSO Triggered Methylene Insertion and C(sp)-C(sp)-H-C(sp) Bond Formation to Access Functional Bis-Heterocycles.

Metal-free insertion of a methylene group was achieved for the construction of a new C(sp)-C(sp)-H-C(sp) bond in order to prepare novel bis-heterocyclic scaffolds. The complete mechanistic investigations included experimental study and DFT calculations, and various symmetric and unsymmetric bis-pyrazoles as well as other pyrazole-based bis-heterocyclic molecules were prepared in moderate to high yields. Further modification of the bridged methylene group in the unsymmetric pyrazoles generated a chiral center to extend the scope of this method.

Chemical analysis of saffron by HPLC based crocetin estimation.

Saffron is one of the most expensive and valuable spice having tremendous commercial value in food industry and thus its quality check is of utmost importance. Crocins are unique group of extremely hydrophilic apocarotenoids which are main components of saffron. Crocetin is an aglycone of crocins which do occur naturally in saffron, and is produced in biological system as a bioactive metabolite via hydrolytic cleavage of crocins.

Antiproliferative activity of diarylnaphthylpyrrolidine derivative via dual target inhibition.

Breast cancer is the second leading cause of deaths in women globally. Present communication deals with design and synthesis of a few diarylnaphthyls as possible anti-breast cancer agents. Among the thirty three representatives with significant antiproliferative activity compounds 23 and 50 were quite efficacious against human breast cancer cells.

Functionalization of Alkynes and Alkenes Using a Cascade Reaction Approach: Synthesis of β-Keto Sulfones under Metal-free Conditions.

Here, we are reporting a multicomponent cascade reaction approach for the synthesis of β-keto sulfones by exploiting differential reactivity pattern of substrates under open-atmosphere and metal-free conditions. The coupling partners are aryldiazonium salts, unsaturated compounds, and DABSO. The optimized conditions worked well with both alkenes and alkynes.

In vitro bactericidal activity of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyrone (CHP) against drug-susceptible, drug-resistant and drug-tolerant isolates of Mycobacterium tuberculosis.

Objectives: Tuberculosis (TB) poses a serious global threat to humans. New bactericidal agents that can shorten treatment duration and target drug resistance still remain a top priority in the discovery of anti-TB drugs. The objective of this study was to investigate the bactericidal potential of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyrone (CHP) against drug-susceptible, drug-resistant clinical isolates and drug-tolerant Mycobacterium tuberculosis.

Binary and ternary solid dispersions of an anticancer preclinical lead, IIIM-290: In vitro and in vivo studies.

The objective of this study was to formulate an anticancer preclinical lead, IIIM-290, loaded in solid dispersions to enhance its solubility, dissolution, and oral pharmacokinetics. IIIM-290 is an in-house preclinical anticancer lead prepared by semisynthetic modification of the natural product rohitukine. It is an orally bioavailable Cdk inhibitor showing efficacy in xenograft models of pancreatic, colon and leukemia cancer.

Fungal endophytes of Plumbago zeylanica L. enhances plumbagin content.

Background: Plumbagin is one of the pharmaceutically important biomolecule with anticancer potential. Among the plants reported to produce plumbagin, P. zeylanica topped the list.

Isolation, Synthesis And Structure Determination Of Cannabidiol Derivatives And Their Cytotoxic Activities.

In a continuing effort to explore the structural diversity and pharmacological activities of natural products based scaffolds, herein, we report the isolation, synthesis, and structure determination of cannabidiol and its derivatives along with their cytotoxic activities. Treatment of cannabidiol () with acid catalyst POCl afforded a new derivative along with six known molecules -, and, . The structure of was elucidated by extensive spectroscopic analyses and DFT calculations of the NMR and ECD data.

Rottlerin is a pan phosphodiesterase inhibitor and can induce neurodifferentiation in IMR-32 human neuroblastoma cells.

Phosphodiesterases are promising targets for pharmacological intervention against various diseases. There are already inhibitors of PDE3, PDE4 and PDE5 as approved drugs. However there is an unmet need to discover new chemical scaffolds as PDE inhibitors.

Isolation of depsipeptides and optimization for enhanced production of valinomycin from the North-Western Himalayan cold desert strain Streptomyces lavendulae.

Exploration of microbial dynamics of Streptomyces lavendulae ACR-DA1, a psychrotrophic isolate from the North-Western Himalayan cold desert, was carried out using matrix-assisted laser desorbtion ionisation-time of flight mass spectrometer. Valinomycin was found as a major produce and cyclic depsipeptide montanastatin as a minor produce. The yield of the valinomycin was found to be 0.

Community structure, spatial distribution, diversity and functional characterization of culturable endophytic fungi associated with Glycyrrhiza glabra L.

A total of 266 endophytic fungal isolates were recovered from 1019 tissue segments of Glycyrrhiza glabra collected from four different locations in the North-Western Himalayas. The endophytes grouped into 21 genera and 38 different taxa. The host had strong affinity for the genus Phoma, followed by Fusarium.

CYP enzymes, expressed within live human suspension cells, are superior to widely-used microsomal enzymes in identifying potent CYP1A1/CYP1B1 inhibitors: Identification of quinazolinones as CYP1A1/CYP1B1 inhibitors that efficiently reverse B[a]P toxicity and cisplatin resistance.

Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in 'suspension' for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents.