Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling.

Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers. We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naive pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumor sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor.

Recent advances and structure-activity relationship studies of DPP-4 inhibitors as anti-diabetic agents.

Diabetes mellitus (DM) is one of the largest public health problems worldwide and in the last decades various therapeutic targets have been investigated. For the treatment of type-2 DM (T2DM), dipeptidyl peptidase-4 (DPP-4) is one of the well reported target and has established safety in terms of cardiovascular complexicity. Preclinical and clinical studies using DPP-4 inhibitors have demonstrated its safety and effectiveness and have lesser risk of associated hypoglycaemic effect making it suitable for elderly patients.

The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma.

Background: A total of 30-40% of diffuse large B cell lymphoma (DLBCL) patients will either not respond to the standard therapy or their disease will recur. The first-line treatment for DLBCL is rituximab and combination chemotherapy. This treatment involves the chemotherapy-induced recruitment of tumor-associated macrophages that recognize and kill rituximab-opsonized DLBCL cells.

Nanotechnology-based Drug Delivery of Topical Antifungal Agents.

Among the various prominent fungal infections, superficial ones are widespread. A large number of antifungal agents and their formulations for topical use are commercially available. They have some pharmacokinetic limitations which cannot be retracted by conventional delivery systems.

Preclinical to Clinical Profile of as Antidiabetic Therapeutics.

Natural product substances have historically served as the most significant source of new leads for pharmaceutical development. Presently, drug discovery and development have adopted rational approaches to explore herbal resources for treating lifestyle-related diseases such as diabetes. For the treatment of diabetes, has been extensively studied for evaluation of its antidiabetic potential using various and models.

Prospective mode of action of Ivermectin: SARS-CoV-2.

The well-known anti-helminthic drug ivermectin (IVM) has been established as an example of drug repurposing for the management of SARS-CoV-2 infection. Various study has been done to understand the inhibitory mechanism of IVM against SARS-CoV-2 targets. Broadly, IVM has been categorized as a host-directed agent and the proposed mechanism involves inhibition of the IMPα/ß1-mediated nuclear import of viral proteins.

Protein Informatics and Vaccine Development: Cancer Case Study.

Clinical translation is a challenging step in the development of cancer vaccines and is found to be related to the complex nature of cancer immunology. Vaccine-based therapeutic strategies for cancer have gained consideration with the advent of vaccine technology as well as an understanding of cancer immunology. Immunotherapy has been widely used in the treatment of cancer.

Artificial intelligence and machine-learning approaches in structure and ligand-based discovery of drugs affecting central nervous system.

CNS disorders are indications with a very high unmet medical needs, relatively smaller number of available drugs, and a subpar satisfaction level among patients and caregiver. Discovery of CNS drugs is extremely expensive affair with its own unique challenges leading to extremely high attrition rates and low efficiency. With explosion of data in information age, there is hardly any aspect of life that has not been touched by data driven technologies such as artificial intelligence (AI) and machine learning (ML).

Non-cancer to anti-cancer: investigation of human ether-a-go-go-related gene potassium channel inhibitors as potential therapeutics.

Background: The expression of hERG K channels is observed in various cancer cells including epithelial, neuronal, leukemic, and connective tissue. The role of hERG potassium channels in regulating the growth and death of cancer cells include cell proliferation, survival, secretion of proangiogenic factors, invasiveness, and metastasis.

Methods: In the reported study, an attempt has been made to investigate some non-cancer hERG blockers as potential cancer therapeutics using a computational drug repurposing strategy.

QSAR Studies to Predict Activity of HSP90 Inhibitors.

Heat shock protein 90 (HSP90) is a multichaperone complex that mediates the maturation and stability of a variety of oncogenic signaling proteins. HSP90 has emerged as a promising target for the development of anticancer agents. Heterocyclic chemical moieties with HSP90 inhibitory activity were studied continuously during the last decades, and resulting data were applied by medicinal chemists to design and develop new drugs.

Chromones: Privileged scaffold in anticancer drug discovery.

In the design and discovery of anticancer drugs, various natural heterocyclic scaffolds have attracted considerable interest as privileged structures. For rational drug design, some of the natural scaffolds such as chromones have exhibited wide acceptability due to their drug-like properties. Among the approved anticancer drugs, the scaffolds with high selectivity for a small group of closely related targets are of importance.

Safe and Effective Kinase Inhibitors for the Treatment of Gynecological Cancers: In Silico Approach.

Aims: This study aimed at studying various types of gynecological cancers and the available therapeutics to investigate safe and effective drugs.

Background: Cancer is the most common cause of mortality throughout the world. When the statistics are being considered for gynecological cancers, ovarian, cervical, and uterine cancers are among the most prevalent types.

Natural Product Databases and Tools for Anti-cancer Drug Discovery.

Throughout the ages, compounds collected and/or isolated from natural sources have been the basic source of medicinal agents against a variety of diseases. The data generated from the extensive experimentation conducted in research labs from all over the world has diversity and complexity, and the challenging task for database creators is to store, represent, and exchange this data. The natural product database is required to be easily accessible for supporting drug discovery efforts.

A systematic review on use of aminoquinolines for the therapeutic management of COVID-19: Efficacy, safety and clinical trials.

Recent global outbreak of the pandemic caused by coronavirus (COVID-19) emphasizes the urgent need for novel antiviral therapeutics. It can be supplemented by utilization of efficient and validated drug discovery approaches such as drug repurposing/repositioning. The well reported and clinically used anti-malarial aminoquinoline drugs (chloroquine and hydroxychloroquine) have shown potential to be repurposed to control the present pandemic by inhibition of COVID-19.

Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort.

Background: Focal irreversible electroporation (IRE) can be used to treat men with localised prostate cancer (PCa) with reduced impact on quality of life (QoL).

Objective: To assess oncological and functional outcomes.

Design, Setting, And Participants: To report on a prospective database of patients undergoing primary IRE between February 2013 and August 2018.

Cinnamaldehyde Analogs: Docking Based Optimization, COX-2 Inhibitory In Vivo and In Vitro Studies.

Background: In the past decade CADD has emerged as a rational approach in drug development so with the help molecular docking approach we planned to perform virtual screening of the designed data set of Schiff bases of cinnamaldehyde. The research work will be helpful to put some light on the drug receptor interactions required for anti-inflammatory activity.

Methods: For carrying out virtual screening of the developed cinnamaldehyde Schiff base data set, AutoDock 4.

N-Substituted Aryl Sulphonamides as Potential Anti-Alzheimer's Agents: Design, Synthesis and Biological Evaluation.

Introduction: A novel series of multifunctional anti-Alzheimer's agents based on Nsubstituted aryl sulphonamides were designed and synthesized. During in vivo moderate to good anti- Alzheimer's Disease (AD) activity was observed as correlated by the modulation of some selected biochemical markers of AD as well as during behavioral assessment.

Methods: Among the series, some compounds have shown multi-functional potency by inhibition of Acetylcholinesterase (AChE), Scopolamine induced oxidative stress and were found comparable to the standard drug.

Designing of Selective γ-Secretase Inhibitory Benzenesulfonamides through Comparative In Vitro and In Silico Analysis.

Background: In Alzheimer's disease (AD), the gene mutations have been identified in the amyloid precursor protein (APP), the presenilin-1 (PS1) and -2 (PS2) genes. APP is a transmembrane protein which gets cleaved by α- and β- secretase enzymes and releases Aβ peptides which forms senile plaques in brain tissue. It contributes for local inflammatory response, subsequent oxidative stress, biochemical changes and neuronal death.

GENIUS In Silico Screening Technology for HCV Drug Discovery.

The various reported in silico screening protocols such as molecular docking are associated with various drawbacks as well as benefits. In molecular docking, on interaction with ligand, the protein or receptor molecule gets activated by adopting conformational changes. These conformational changes cannot be utilized to predict the 3D structure of a protein-ligand complex from unbound protein conformations rigid docking, which necessitates the demand for understanding protein flexibility.

HCV Inhibitors: Role of Compounds from Botanical Sources.

The developing number of hepatitis C virus infected cases worldwide has threatened people's health. The available therapeutic options have low specificity, side effects and high rate of drug resistance and thus potentiate the need for novel effective anti-HCV drugs. Agents obtained from natural sources offer an enormous scope of structural diversity and broad therapeutic range of coverage.

Heterocyclic Secretase Inhibitors for the Treatment of Alzheimer's Disease: An Overview.

Alzheimer's disease (AD), the most common neurodegenerative disorder and demands to find a way for prevention and delayed onset. The development of therapeutics for AD is based on the amyloid cascade hypothesis (vaccines, β- and γ-Secretase inhibitors), or targeting tau and neurofibrillary tangle formation, neuroinflammation, etc. Cholinesterase, BACE-1, amyloid-β 1-42, γ and β-Secretase, Phosphodiesterase type IV (PDE4) inhibitors are the reported treatment strategies.

3D-QSAR and docking studies on a series of benzothiadiazine derivatives as genotype 1 HCV polymerase inhibitors.

The Benzothiadiazine derivatives have been regarded as a novel class of HCV genotype 1 polymerase inhibitors. To explore the relationship between the structures of substituted Benzothiadiazine derivatives and their inhibitory activities against HCV, 3D-QSAR and molecular docking studies were performed on a dataset of ninty-eight compounds. The 3D-QSAR models resulted from seventy-eight molecules in the training set gave q(2) value of 0.

Synthesis, in vitro and in silico NS5B polymerase inhibitory activity of benzimidazole derivatives.

Hepatitis C virus (HCV) NS5B polymerase is the key replicating protein of the virus and thus an attractive target for drug development. Here we report on the synthesis and biological evaluation of a new series of benzimidazole derivatives as HCV NS5B inhibitors. This yielded compound 6b and 6d bearing 2-(2-benzyloxy)phenyl and 2-(4-methylbenzyloxy)phenyl moieties, respectively, as promising leads.

Current perspective of HCV NS5B inhibitors: a review.

Hepatitis C virus (HCV) infection has emerged as one of the most significant disease to affect humans. Despite its large medical and economical impact, there are no vaccines or efficient therapies without major side effects. The HCV non-structural protein 5B (NS5B) is the RNA-dependent RNA polymerase responsible for the complete copy of the RNA viral genome and is a target of choice for the development of anti-HCV drugs.