A5034610653- Retinal Diseases and Treatments
- Angiogenesis and VEGF in Cancer
- Natural product bioactivities and synthesis
- Glaucoma and retinal disorders
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Phytochemical Studies and Bioactivities
- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Synthesis and Biological Activity
- Diabetes and associated disorders
- Oxidative Organic Chemistry Reactions
- Natural Compounds in Disease Treatment
- Nitric Oxide and Endothelin Effects
- Ocular Oncology and Treatments
- Endoplasmic Reticulum Stress and Disease
- Corneal Surgery and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ubiquitin and proteasome pathways
- Retinal and Optic Conditions
- Ovarian cancer diagnosis and treatment
- Cancer-related Molecular Pathways
- Biological Stains and Phytochemicals
- Intracranial Aneurysms: Treatment and Complications
- Chromatography in Natural Products
Beckman Research Institute
2020-2023
City of Hope
2020-2023
Indiana University – Purdue University Indianapolis
2012-2019
Indiana University School of Medicine
2012-2019
Hypertension Institute
2014-2019
Cairo University
2015
Gachon University
2015
AstraZeneca (India)
2014
Indiana University
2014
University School
2014
Aminopyrazinamides originated from a high throughput screen targeting the Mycobacterium smegmatis (Msm) GyrB ATPase. This series displays chemical tractability, robust structure-activity relationship, and potent antitubercular activity. The crystal structure of Msm in complex with one aminopyrazinamides revealed promising attributes specificity against other broad spectrum pathogens selectivity eukaryotic kinases due to novel interactions at hydrophobic pocket, unlike known inhibitors....
A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition DNA Gyrase B (GyrB) ATPase. Evaluation binding mode thiazolopyridines in Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration side chains at ring C-5 position access ribose/solvent pocket. Potent compounds IC50 ≤ 1 nM and Mtb MIC 0.1 μM were obtained certain combinations heterocycles C-6 core. Substitutions also...
Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes blindness. Cremastranone is an antiangiogenic, naturally occurring homoisoflavanone with efficacy in retinal choroidal neovascularization models antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure-activity relationship study to develop more potent...
The homoisoflavanone cremastranone is synthesized for the first time and shown to block human retinal endothelial cell angiogenesis <italic>in vitro</italic>.
Abstract Ocular neovascularization underlies major blinding eye diseases such as “wet” age‐related macular degeneration (AMD). Despite the successes of treatments targeting vascular endothelial growth factor (VEGF) pathway, resistant and refractory patient populations necessitate discovery new therapeutic targets. Using a forward chemical genetic approach, we identified heme synthesis enzyme ferrochelatase (FECH) necessary for angiogenesis in vitro vivo . FECH is overexpressed wet AMD eyes...
KIF14 (kinesin family member 14) is a mitotic kinesin and an important oncogene in several cancers. Tumor expression levels are independently predictive of poor outcome, cancer cells can modulate metastatic behavior by maintaining appropriate cell adhesion migration proteins at the membrane. Thus exciting potential therapeutic target. Understanding KIF14's regulation crucial to development effective selective therapies block its tumorigenic function(s). We previously determined that close...
Preventing pathological ocular angiogenesis is key to treating retinopathy of prematurity, diabetic and age-related macular degeneration. At present there no small molecule drug on the market target this process hence a pressing need for developing novel molecules that can replace or complement surgical biologic therapies these neovascular eye diseases. Previously, an antiangiogenic homoisoflavanone was isolated from bulb medicinal orchid, Cremastra appendiculata. In study, we synthesis...
Excessive blood vessel formation in the eye is implicated wet age-related macular degeneration, proliferative diabetic retinopathy, neovascular glaucoma, and retinopathy of prematurity, which are major causes blindness. Small molecule antiangiogenic drugs strongly needed to supplement existing biologics. Homoisoflavonoids have been previously shown potent antiproliferative activities endothelial cells over other cell types. Moreover, they demonstrated a strong potential vitro vivo animal...
A loss of functional beta cell mass is a final etiological event in the development frank type 2 diabetes (T2D). To preserve or expand cells and therefore treat/prevent T2D, growth factors have been considered therapeutically but largely failed to achieve robust clinical success. The molecular mechanisms preventing activation mitogenic signaling pathways from maintaining during T2D remain unknown. We speculated that endogenous negative effectors cascades impede survival/expansion. Thus, we...
Mycobacterium tuberculosis (Mtb) DNA gyrase ATPase was the target of a drug discovery program. The low specific activity Mtb prompted use smegmatis (Msm) enzyme as surrogate for lead generation, since it had 20-fold higher activity. Addition GyrA or did not significantly increase Msm GyrB ATPase, and an assay developed using alone. Inhibition correlated well with inhibition supercoiling across three chemical scaffolds, justifying its use. As IC50 compounds approached concentration, assays...
Avoiding the loss of functional beta cell mass is critical for preventing or treating diabetes. Currently, molecular mechanisms underlying death are partially understood, and there a need to identify new targets developing novel therapeutics treat Previously, our group established that Mig6, an inhibitor EGF signaling, mediates under diabetogenic conditions. The objective here was clarify linking stimuli by investigating Mig6-interacting proteins. Using co-immunoprecipitation spectrometry,...
ABSTRACT A loss of functional beta cell mass is a final etiological event in the development frank type 2 diabetes (T2D). To preserve or expand cells and therefore treat/prevent T2D, growth factors have been considered therapeutically but largely failed to achieve robust clinical success. The molecular mechanisms preventing activation mitogenic signaling pathways from maintaining during T2D remain unknown. We speculated that endogenous negative effectors cascades impede survival/expansion....