Browse Items · NEOMED Bibliography Database

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…

Effects of gelucire content on stability, macrophage interaction and blood circulation of nanoparticles engineered from nanoemulsions.

The main objective of the study is to investigate the efficacy of Gelucire 44/14 (gelucire) in facilitating formation of cetyl alcohol (CA)-based nanoparticle (NP) and to assess the effects on key NP properties and functions. NPs from oil-in-water…

Biocompatibility, efficacy and biodistribution of Gelucire-stabilized nanoparticles engineered for docetaxel delivery.

Docetaxel is a potent anticancer agent that will benefit greatly from alternative delivery systems that can overcome several reported adverse effects due to the drug itself and/or the solvent system in the current clinical formulation. In this…

Tags: *Biocompatible Materials, *Nanoparticles, 2012, Animals, Antineoplastic Agents/*administration & dosage/pharmacokinetics/pharmacology, Bi Lipeng, Department of Pharmaceutical Sciences, Docetaxel, Geldenhuys Werner J, Journal of nanoscience and nanotechnology, Macrophage Activation/drug effects, NEOMED College of Pharmacy, Oyewumi Moses O, Platelet Aggregation/drug effects, Rats, Reactive Oxygen Species/metabolism, Taxoids/*administration & dosage/pharmacokinetics/pharmacology, Tissue Distribution, Wehrung Daniel

Antitumor efficacy and tolerability of systemically administered gallium acetylacetonate-loaded gelucire-stabilized nanoparticles.

The widespread clinical success with most gallium compounds in cancer therapy is markedly hampered by lack of tumor specific accumulation, poor tumor permeability and undesirable toxicity to healthy tissues. The aim of this work was to investigate…

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…

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…

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

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

Development and validation of a novel RP-HPLC method for the analysis of reduced glutathione.

The objective of this study was the development, optimization, and validation of a novel reverse-phase high-pressure liquid chromatography (RP-HPLC) method for the quantification of reduced glutathione in pharmaceutical formulations utilizing simple…

Tags: 2012, Chromatography, Geldenhuys Werner J, Glutathione/*analysis, High Pressure Liquid/*methods, Journal of chromatographic science, Limit of Detection, Linear Models, Nanoparticles/chemistry, Pharmaceutical Preparations/chemistry, Reproducibility of Results, Reverse-Phase/*methods, Spectrophotometry, Sutariya Vijaykumar, Ultraviolet, Wehrung Daniel

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…

A quantitative LC-MS/MS method for determination of thiazolidinedione mitoNEET ligand NL-1 in mouse serum suitable for pharmacokinetic studies.

Thiazolidinedione (TZD) compounds have shown promise as antidiabetic, antibiotics, antifungal and neuroprotective agents. The mitochondrial effect of a novel mitoNEET ligand, NL-1…

Tags: %CV, %RE, 1-Methyl-4-phenyl-1, 2, 2014, 3, 3-thiazolidine-2, 4-dione, 5-[3, 5-[4-hydroxy-3, 5-di-tert-butyl-4-hydroxyphenyl)methyl]-1, 5-dimethyl-phenyl)methyl]thiazolidine-2, 6-tetrahydropyridine, Anderson David J, Animals, Carroll Richard T, Carry-over, Chromatography, Department of Internal Medicine, Geldenhuys Werner J, High Pressure Liquid/*methods, internal standard, IS, Jogiraju Harini, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, LC-MS/MS, Limit of Detection, Lin Li, LLOQ, lower limit of quantification, Methanol, Mice, mitoNEET, Mouse serum, MPTP, MRM, multiple reaction monitoring, NEOMED College of Medicine, NL-1, NL-2, Pedada Kiran K, percent coefficient of variation, peroxisome proliferator activated receptor-gamma, pharmacokinetic, PK, PPAR-gamma, QC, Quality Control, relative error, relative matrix effect, RME, SD, standard deviation, Tandem Mass Spectrometry/*methods, thiazolidinedione, Thiazolidinedione (TZD), Thiazolidinediones/*blood, TZD, Zhou Xiang

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

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

Engineering triiodothyronine (T3) nanoparticle for use in ischemic brain stroke.

A potential means of pharmacological management of ischemic stroke is rapid intervention using potent neuroprotective agents. Thyroid hormone (T3) has been shown to protect against ischemic damage in middle cerebral artery occlusion (MCAO) model of…

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

Alteration of hepatic proinflammatory cytokines is involved in the resveratrol-mediated chemoprevention of chemically-induced hepatocarcinogenesis.

Hepatocellular carcinoma (HCC), one of the most common cancers in the world, is a leading cause of cancerrelated mortality. HCC develops most frequently in the background of oxidative stress and chronic hepatic inflammation due to viral infections,…

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…

Generation and characterization of ATP analog-specific protein kinase Cdelta.

To better study the role of PKCdelta in normal function and disease, we developed an ATP analog-specific (AS) PKCdelta that is sensitive to specific kinase inhibitors and can be used to identify PKCdelta substrates. AS PKCdelta showed nearly 200…

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…

Development and validation of an LC-MS/MS method for determination of the L-type voltage-gated calcium channel/NMDA receptor antagonist NGP1-01 in mouse serum.

NGP1-01 (8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane) is a heterocyclic cage compound with multifunctional calcium channel blocking activity that has been demonstrated to be neuroprotective in several neurodegenerative…

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

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…

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

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

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

Designing drugs with multi-target activity: the next step in the treatment of neurodegenerative disorders.

INTRODUCTION: Neurodegenerative diseases have had devastating effects on patients' quality of life. These complex diseases have several pathways that are affected to initiate cell death. Current therapies, designed to address only a single target,…

Tags: *Drug Design, 2013, Central Nervous System Diseases/*drug therapy, Clinical Trials as Topic, Expert opinion on drug discovery, Geldenhuys Werner J, Humans, Neurodegenerative Diseases/*drug therapy, Neuroprotective Agents/*chemistry/therapeutic use, Van der Schyf Cornelis J

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

3D-Quantitative structure-activity relationship and docking studies of the tachykinin NK3 receptor.

The tachykinin NK(3) receptor (NK(3)R) is a novel drug target for schizophrenia and drug abuse. Since few non-peptide antagonists of this G protein-coupled receptor are available, we have initiated this study to gain a better understanding of the…

Tags: *Quantitative Structure-Activity Relationship, 2011, Binding Sites, Bioorganic & medicinal chemistry letters, Computer Simulation, Drug Design, Geldenhuys Werner J, Humans, Ligands, Models, Molecular, Neurokinin-3/*chemistry/metabolism, Protein Structure, Quinolines/chemistry, Receptors, Simmons Mark A, Tertiary

3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (sigma1) receptor.

Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D…

Tags: *Quantitative Structure-Activity Relationship, 2013, Amines/*chemistry/metabolism, Aza Compounds/chemistry, Binding Sites, Bioorganic & medicinal chemistry letters, Geldenhuys Werner J, Kinetics, Malan Sarel F, Molecular Docking Simulation, Novotny Nicholas, Protein Binding, Protein Structure, Receptors, sigma/*chemistry/metabolism, Tertiary, Van der Schyf Cornelis J

3D-QSAR and docking studies on transforming growth factor (TGF)-beta receptor 1 antagonists.

The transforming growth factor-beta (TGF-beta) is part of a family of cytokines which regulate various signaling pathways such as cell development, growth, and tissue injury. Although several studies have been published describing the synthesis of…

Tags: 2010, Bioorganic & medicinal chemistry letters, Geldenhuys Werner J, Models, Molecular, Nakamura Hiroshi, Quantitative Structure-Activity Relationship, Receptors, Transforming Growth Factor beta/*antagonists & inhibitors

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

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…

Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases.

Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by…

Tags: 2017, Animals, Cardiovascular Diseases/drug therapy/*enzymology, Darvesh Altaf S, Department of Pharmaceutical Sciences, Department of Pharmacy Practice, Drug Discovery Today, Geldenhuys Werner J, Humans, Lin Li, Lipoprotein Lipase/chemistry/*metabolism, Metabolic Diseases/drug therapy/*enzymology, NEOMED College of Graduate Studies, NEOMED College of Pharmacy, Sadana Prabodh

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

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…

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

Exploring Adenosine Receptor Ligands: Potential Role in the Treatment of Cardiovascular Diseases.

Cardiovascular diseases remain the number one diseases affecting patients' morbidity and mortality. The adenosine receptors are G-protein coupled receptors which have been of interest for drugs target for the treatment of multiple diseases ranging…

A novel biomechanical analysis of gait changes in the MPTP mouse model of Parkinson's disease.

Parkinson's disease (PD) is an age-associated neurodegenerative disorder hallmarked by a loss of mesencephalic dopaminergic neurons. Accurate recapitulation of the PD movement phenotype in animal models of the disease is critical for understanding…

Tags: 2015, Behavior, Department of Anatomy & Neurobiology, Dluzen Dean E, Gait, Geldenhuys Werner J, Gender-bias, Guseman Tamara L, Locomotion, MPTP, NEOMED College of Medicine, PeerJ, Pienaar Ilse S, Young Jesse W

A scaffold hopping approach to identify novel monoamine oxidase B inhibitors.

Monoamine oxidase B (MAO-B) inhibitors are used to treat Parkinson's disease. In this study, we searched for novel MAO-B inhibitors using a scaffold hopping approach based on our experience with the thiazolidinedione (TZD) class of compounds as MAO-B…

Tags: *Monoamine Oxidase/chemistry/metabolism, 2012, Benzofurans/chemistry/pharmacology, Bioorganic & medicinal chemistry letters, Carroll Richard T, Enzyme Activation/drug effects, Flavonoids/chemistry/pharmacology, Funk Max O, Geldenhuys Werner J, Humans, Inhibitory Concentration 50, Models, Molecular, Molecular Structure, Monoamine Oxidase Inhibitors/*chemistry/*pharmacology, Protein Binding/drug effects, Small Molecule Libraries, Structure-Activity Relationship, Van der Schyf Cornelis J

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…

A novel binding assay identifies high affinity ligands to the rosiglitazone binding site of mitoNEET.

A novel outer mitochondrial membrane protein containing [2Fe-2S] clusters, mitoNEET was first identified through its binding to the anti-diabetic drug pioglitazone. Pioglitazone belongs to a family of drugs that are peroxisome proliferator-activated…

Tags: 2011, Awale Prabha S, Binding Sites/drug effects, Bioorganic & medicinal chemistry letters, Carroll Richard T, Dose-Response Relationship, Drug, Funk Max O, Geldenhuys Werner J, Ligands, Lin Li, Mitochondrial Proteins/*antagonists & inhibitors/metabolism, Molecular Structure, Recombinant Proteins/antagonists & inhibitors/metabolism, Rosiglitazone, Stereoisomerism, Structure-Activity Relationship, Thiazolidinediones/chemical synthesis/chemistry/*pharmacology

Browse Items (61 total)