Browse Items · NEOMED Bibliography Database

Virtual screening to identify novel antagonists for the G protein-coupled NK3 receptor.

The NK(3) subtype of tachykinin receptor is a G protein-coupled receptor that is a potential therapeutic target for several neurological diseases, including schizophrenia. In this study, we have screened compound databases for novel NK(3) receptor…

The serotonin 5-HT6 receptor: a viable drug target for treating cognitive deficits in Alzheimer's disease.

The serotonin 6 receptor is attracting attention as an etiological contributor in cognition deficits in diseases such as Alzheimer's disease, anxiety/depression and schizophrenia. In this review, we discuss the role of this recently discovered G…

Tags: 2009, Alzheimer Disease/*complications, Animals, Biological, Cognition Disorders/*drug therapy/*etiology, Drug Design, Expert review of neurotherapeutics, Geldenhuys Werner J, Humans, Models, Receptors, Serotonin Antagonists/chemistry/*therapeutic use, Serotonin/*metabolism, Structure-Activity Relationship, Van der Schyf Cornelis J

The emergence of designed multiple ligands for neurodegenerative disorders.

The incidence of neurodegenerative diseases has seen a constant increase in the global population, and is likely to be the result of extended life expectancy brought about by better health care. Despite this increase in the incidence of…

Tags: *Drug Design, *Ligands, 2011, Amyloid beta-Peptides/metabolism, Antiparkinson Agents/therapeutic use, Carroll Richard T, Clinical Trials as Topic, Geldenhuys Werner J, Humans, Molecular Structure, Neurodegenerative Diseases/*drug therapy, Neuroprotective Agents/*therapeutic use, Progress in neurobiology, Van der Schyf Cornelis J, Youdim Moussa B H

The blood-brain barrier choline transporter.

Drug delivery to the brain is made difficult by the blood-brain barrier (BBB) which is selectively permeable to organic drug compounds. Several membrane solute and nutrient transporters are expressed in the BBB vasculature, which may be utilized as…

Tags: 2012, Allen David D, Animals, Blood-Brain Barrier/drug effects/*metabolism, Central nervous system agents in medicinal chemistry, Drug Delivery Systems/*methods, Geldenhuys Werner J, Humans, Membrane Transport Proteins/*metabolism, Organic Cation Transport Proteins/metabolism, Organic Cation Transporter 1/metabolism, Organic Cation Transporter 2

Synthesis and Biological Evaluation of Pentacycloundecylamines and Triquinylamines as Voltage-Gated Calcium Channel Blockers.

Preclinical studies for neurodegenerative diseases have shown a multi-targeted approach to be successful in the treatment of these complex disorders with several pathoetiological pathways. Polycyclic compounds, such as NGP1-01 (7a), have demonstrated…

Structure-based design of a thiazolidinedione which targets the mitochondrial protein mitoNEET.

Several PPAR-gamma agonists containing a thiazolidinedione moiety (referred to as glitazones) have been proposed to be neuroprotective and appear to alter mitochondrial function. Recently, a search for mitochondrial proteins that bind pioglitazone…

Structure-activity relationships of pentacycloundecylamines at the

Prompted by our interest in neuroprotective agents with multiple mechanisms of action, we assessed the structure-activity relationship of a series of pentacycloundecylamine derivatives previously shown to have both L-type calcium channel blocking…

Structure-activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B.

The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type compounds for monoamine oxidase A and B inhibition activity. These compounds were able to…

Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator.

Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in…

Serotonin 5-HT6 receptor antagonists for the treatment of Alzheimer's disease.

Recently, the serotonin 5-HT(6) receptor has been identified as a drug target for attenuating cognitive deficits associated with Alzheimer's disease (AD). Additionally, this receptor may also play a role in schizophrenia, anxiety and obesity. Reports…

Tags: 2008, Alzheimer Disease/*drug therapy, Current topics in medicinal chemistry, Geldenhuys Werner J, Humans, Molecular Structure, Nootropic Agents/chemistry/*therapeutic use, Receptors, Serotonin Antagonists/chemistry/*therapeutic use, Serotonin/*metabolism, Van der Schyf Cornelis J

Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway.

The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase…

Tags: 2014, Alazizi Adnan, Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology, Antitumor, AXL, Bioorganic & medicinal chemistry letters, Cell Line, Cell Proliferation/drug effects, Cell Survival/drug effects, Department of Pharmaceutical Sciences, Dose-Response Relationship, Drug, Drug Resistance, Drug Screening Assays, Gallium, Gallium-resistance, Gallium/pharmacology, Geldenhuys Werner J, Humans, Lin Li, Liva Sophia, Lung cancer, Lung Neoplasms/drug therapy/*enzymology/*pathology, Molecular Structure, Naphthalenes/chemistry/*pharmacology, NEOMED College of Pharmacy, Neoplasm/drug effects, Oyewumi Moses O, Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism, Pyrazoles/chemistry/*pharmacology, Quinolines/chemistry/*pharmacology, Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism, Structure-Activity Relationship, Tetrazoles/chemistry/*pharmacology, Tumor, Virtual screening

Role of serotonin in Alzheimer's disease: a new therapeutic target?

Mounting evidence accumulated over the past few years indicates that the neurotransmitter serotonin plays a significant role in cognition. As a drug target, serotonin receptors have received notable attention due in particular to the role of several…

Tags: 2011, Alzheimer Disease/*drug therapy/*metabolism, Alzheimer's Disease – Drug Therapy, Alzheimer's Disease – Metabolism, Animals, Cell Surface – Metabolism, Clinical Trials, Clinical Trials as Topic, CNS drugs, Drug Evaluation, Geldenhuys Werner J, Humans, Preclinical, Receptors, Serotonin – Pharmacodynamics, Serotonin – Therapeutic Use, Serotonin/*metabolism, Serotonin/*pharmacology/*therapeutic use, Van der Schyf Cornelis J

Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization.

Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that…

Polycyclic compounds: ideal drug scaffolds for the design of multiple mechanism drugs?

Recently there has been a resurging interest in developing multi-functional drugs to treat diseases with complex pathological mechanisms. Such drug molecules simultaneously target multiple etiologies that have been found to be important modulators in…

Tags: *Drug Design, 2009, Adamantane/chemistry/pharmacology, Animals, Central Nervous System Diseases/*drug therapy, Geldenhuys Werner J, Humans, Molecular Structure, Neuroprotective Agents/chemistry/*pharmacology/therapeutic use, Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, Polycyclic Compounds/*chemistry/pharmacology/therapeutic use, Psychotropic Drugs/chemistry/*pharmacology/therapeutic use, Quantitative Structure-Activity Relationship, Van der Schyf Cornelis J

Pharmacotherapy of Alzheimer's disease: current and future trends.

Alzheimer's disease (AD) and its related dementia has shown an alarming rise in the global population. Although considerable efforts have been made to develop effective therapeutic agents for AD therapy, drug development has not met significant…

Tags: 2015, Alzheimer Disease/*drug therapy, Alzheimer's disease, Anti-Inflammatory Agents, Antioxidants, cholinesterase inhibitors, Darvesh Altaf S, dementia, Department of Pharmaceutical Sciences, Drug Therapy/*methods/*trends, Expert review of neurotherapeutics, Geldenhuys Werner J, Humans, immunotherapy, memantine, multi-targeted drugs, natural products, NEOMED College of Pharmacy, Pharmacotherapy

Parkinson's disease biomarker: a patent evaluation of WO2013153386.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative movement disorder resultant from the loss of dopaminergic neurons in the brain. There is an urgent need for effective biomarkers that can be used in the early diagnosis of PD.…

Oxidative stress and Alzheimer's disease: dietary polyphenols as potential therapeutic agents.

Oxidative stress has been strongly implicated in the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). In recent years, antioxidants - especially those of dietary origin - have been suggested as possible agents useful…

Tags: 2010, Alzheimer Disease/*physiopathology/*therapy, Animals, Antioxidants/*administration & dosage/chemistry/pharmacology, Bishayee Anupam, Carroll Richard T, Darvesh Altaf S, Department of Pharmaceutical Sciences, Expert review of neurotherapeutics, Flavonoids/*administration & dosage/chemistry/pharmacology, Geldenhuys Werner J, Humans, Mitochondria/drug effects/physiology, NEOMED College of Pharmacy, Neurodegenerative Diseases/physiopathology, Oxidative Stress/drug effects/*physiology, Phenols/*administration & dosage/chemistry/pharmacology, Polyphenols, Van der Schyf Cornelis J

Osteoactivin inhibition of osteoclastogenesis is mediated through CD44-ERK signaling.

Osteoactivin is a heavily glycosylated protein shown to have a role in bone remodeling. Previous studies from our lab have shown that mutation in Osteoactivin enhances osteoclast differentiation but inhibits their function. To date, a classical…

Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.

Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative…

Novel multifunctional anti-Alzheimer drugs with various CNS neurotransmitter targets and neuroprotective moieties.

Traditionally, drug design programs are focused on optimizing the specificity of lead compounds against a carefully selected drug target. Disappointingly, this approach to discover a "magic bullet" drug has not met with the expected success for CNS…

Novel models for assessing blood-brain barrier drug permeation.

INTRODUCTION: The blood-brain barrier (BBB) is a selectively permeable micro-vascular unit which prevents many central nervous system (CNS)-targeted compounds from reaching the brain. A significant problem in CNS drug development is the ability to…

Tags: *Capillary Permeability, 2012, Allen David D, Animal, Animals, Blood-Brain Barrier/*metabolism, Bloomquist Jeffrey R, Drosophila melanogaster/metabolism, Expert opinion on drug metabolism & toxicology, Geldenhuys Werner J, Grasshoppers/metabolism, High-Throughput Screening Assays, Humans, Models, Pharmaceutical Preparations/*metabolism, Zebrafish/metabolism

Novel compounds that target lipoprotein lipase and mediate growth arrest in acute lymphoblastic leukemia.

Over the past decade, the therapeutic strategies employed to treat B-precursor acute lymphoblastic leukemia (ALL) have been progressively successful in treating the disease. Unfortunately, the treatment associated dyslipidemia, either acute or…

Tags: *Acute lymphoblastic leukemia, *Cancer, *Co-culture model, *Lipids, *Lipoprotein lipase, *Metabolism, 2018, Amides/chemistry/metabolism/pharmacology, Antineoplastic Agents/*chemistry/metabolism/pharmacology, Binding Sites, Bioorganic & medicinal chemistry letters, Cell Line, Cell Proliferation/drug effects, Coculture Techniques, Department of Pharmaceutical Sciences, Department of Pharmacy Practice, Dyslipidemias/complications/metabolism/pathology, Geldenhuys Werner J, Gibson Laura F, Humans, Lipoprotein Lipase/antagonists & inhibitors/*metabolism, Mesenchymal Stem Cells/cytology/metabolism, Molecular Docking Simulation, Nair Rajesh R, NEOMED College of Graduate Studies, NEOMED College of Pharmacy, Piktel Debbie, Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/metabolism/pathology, Protein Binding, Protein Structure, Sadana Prabodh, Serum Albumin/chemistry/metabolism, Tertiary, Tumor

Natural products of dietary origin as lead compounds in virtual screening and drug design.

Natural products have been found to be useful in the treatment of several diseases across the ages. In this article, we review the use of natural products, obtained from dietary sources, as lead compounds in developing novel therapeutic agents. These…

Tags: *Biological Products/pharmacology, *Drug Design, 2012, Animals, Bishayee Anupam, Caffeine/pharmacology, Carroll Richard T, Curcumin/pharmacology, Current pharmaceutical biotechnology, Darvesh Altaf S, Department of Pharmaceutical Sciences, Diet, Geldenhuys Werner J, Genistein/pharmacology, Humans, NEOMED College of Pharmacy, Resveratrol, Stilbenes/pharmacology

Multimodal drugs and their future for Alzheimer's and Parkinson's disease.

This chapter discusses the rationale for developing multimodal or multifunctional drugs (also called designed multiple ligands or DMLs) aimed at disease-modifying treatment strategies for the most common neurodegenerative diseases Alzheimer's and…

Tags: 2011, Alzheimer Disease/*drug therapy/*enzymology/prevention & control, Animals, Combined Modality Therapy/*methods, Forecasting, Geldenhuys Werner J, Humans, International review of neurobiology, Monoamine Oxidase Inhibitors/*pharmacology/therapeutic use, Parkinson Disease/*drug therapy/*enzymology/prevention & control, Van der Schyf Cornelis J

Molecular determinants of blood-brain barrier permeation.

The blood-brain barrier (BBB) is a microvascular unit which selectively regulates the permeability of drugs to the brain. With the rise in CNS drug targets and diseases, there is a need to be able to accurately predict a priori which compounds in a…

Tags: *Drug Delivery Systems, 2015, Adkins Chris E, Animals, Blood-Brain Barrier/*metabolism, Brain/drug effects, Computer Simulation, Geldenhuys Werner J, high-throughput, Humans, in silico, Lockman Paul R, logPS, Mohammad Afroz S, nutrient transporters, Permeability, Therapeutic delivery, Virtual screening

mitoNEET as a novel drug target for mitochondrial dysfunction.

Mitochondrial dysfunction plays an important part in the pathology of several diseases, including Alzheimer's disease and Parkinson's disease. Targeting mitochondrial proteins shows promise in treating and attenuating the neurodegeneration seen in…

Tags: 2014, Animals, Carroll Richard T, Drug Delivery Systems, Drug Discovery Today, Energy Metabolism, Geldenhuys Werner J, Humans, Leeper Thomas C, Mitochondria/*metabolism, Mitochondrial Proteins/chemistry/*metabolism, Protein Conformation, Thiazolidinediones/pharmacology

MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype.

Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur…

Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease affecting movement. To date, there are no currently available therapeutic agents which can prevent or slow disease progression. Here, we evaluated an azobenzene derivative, methyl…

Tags: *MAO-B inhibitor, *methyl yellow, *MPTP mouse model, *Parkinson's disease, *TMRM, 2014, Chembiochem : a European journal of chemical biology, Dluzen Dean E, Geldenhuys Werner J, Kochi Akiko, Lim Mi Hee, Lin Li, Sutariya Vijaykumar, Van der Schyf Cornelis J

Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity.

Intact male CD-1 mice received an injection of testosterone propionate (TP–5 ug), progesterone (P–5 mg), the oil vehicle or remained untreated (control). At 24 hours after hormonal treatments the mice received an injection of methamphetamine (MA–40…

Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease.

A series of compounds related to piperine and antiepilepsirine was screened in a monoamine oxidase A and B assay. Piperine is an alkaloid from the source plant of both black and white pepper grains, Piper nigrum. Piperine has been shown to have a…

In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery.

INTRODUCTION: Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo…

Tags: 2011, Carroll Richard T, Darvesh Altaf S, Department of Pharmaceutical Sciences, Expert opinion on drug discovery, Geldenhuys Werner J, Gudelsky Gary A, Klein Jochen, Meshul Charles K, NEOMED College of Pharmacy, Van der Schyf Cornelis J

Identification of small molecules that bind to the mitochondrial protein mitoNEET.

MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and…

Identification of novel monoamine oxidase B inhibitors by structure-based virtual screening.

Parkinson's disease is a severe debilitating neurodegenerative disorder. Recently, it was shown that the peroxisome proliferating-activator receptor-gamma agonist pioglitazone protected mice from

Tags: 2010, Bioorganic & medicinal chemistry letters, Carroll Richard T, Darvesh Altaf S, Department of Pharmaceutical Sciences, Funk Max O, Geldenhuys Werner J, Models, Molecular, Monoamine Oxidase Inhibitors/chemistry/*pharmacology, Monoamine Oxidase/*drug effects, NEOMED College of Pharmacy, Structure-Activity Relationship, Van der Schyf Cornelis J

Identification of Novel Agents for the Treatment of Brain Metastases of Breast Cancer.

BACKGROUND: Brain cancer from metastasized breast cancer has a high mortality rate in women. The treatment of lesions is hampered in large part by the blood-brain barrier (BBB), which prevents adequate distribution of anti-cancer compounds to brain…

Identification of a novel serum and glucocorticoid regulated kinase-1 (SGK1) ligand from virtual screening.

The serum and glucocorticoid regulated kinase-1 (SGK1) is part of the serine/threonine kinase family and has therapeutic potential in several neurodegenerative diseases such as ischemic stroke and Parkinson's disease. Here we use structure-based…

Tags: 2012, Binding Sites, Bioorganic & medicinal chemistry letters, Department of Pharmaceutical Sciences, Department of Pharmacy Practice, Drug Discovery, Geldenhuys Werner J, Humans, Immediate-Early Proteins/*antagonists & inhibitors/chemistry/metabolism, Ligands, Molecular Docking Simulation, NEOMED College of Graduate Studies, NEOMED College of Pharmacy, Protein Kinase Inhibitors/*chemistry/*pharmacology, Protein-Serine-Threonine Kinases/*antagonists & inhibitors/chemistry/metabolism, Sadana Prabodh, Talasila Phani K

High-content screen using zebrafish (Danio rerio) embryos identifies a novel kinase activator and inhibitor.

In this report we utilized zebrafish (Danio rerio) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD)…

Tags: *Cancer, *Compound library, *Kinase, *Notochord, *Phenotypic screen, *Somites, *Zebrafish, 2017, Aljammal Rowaa, Animals, Antineoplastic Agents/chemistry/pharmacology, Antitumor/methods, Benzoic Acid/chemistry/pharmacology, Bergeron Sadie A, Bioorganic & medicinal chemistry letters, Chen Wei-Chi, Death-Associated Protein Kinases/metabolism, Department of Integrative Medical Sciences, Drug Discovery/*methods, Drug Screening Assays, Embryo, Enzyme Activation/drug effects, Enzyme Activators/*chemistry/*pharmacology, Gaasch Briah L, Geldenhuys Werner J, Hazlehurst Lori A, Mullins Jackie E, NEOMED College of Medicine, Neoplasms/drug therapy/enzymology, Nonmammalian/*drug effects/enzymology, Protein Kinase Inhibitors/*chemistry/*pharmacology, Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism, Yun June, Zebrafish Proteins/antagonists & inhibitors/metabolism, Zebrafish/*embryology

Tags: 2013, Blood-brain barrier, Brain stroke, Department of Pharmaceutical Sciences, Department of Pharmacy Practice, Drug delivery and translational research, Geldenhuys Werner J, Mdzinarishvili Alexander, Nanoparticles, NEOMED College of Graduate Studies, NEOMED College of Pharmacy, Neuroprotection, Sadana Prabodh, Sutariya Vijaykumar, Talasila Phani K, Thyroid hormone

Browse Items (61 total)