A5023158279- Catalytic C–H Functionalization Methods
- Cyclopropane Reaction Mechanisms
- Synthesis and Catalytic Reactions
- Fluorine in Organic Chemistry
- Asymmetric Synthesis and Catalysis
- Catalytic Alkyne Reactions
- Sulfur-Based Synthesis Techniques
- Radical Photochemical Reactions
- Asymmetric Hydrogenation and Catalysis
- Alzheimer's disease research and treatments
- Oxidative Organic Chemistry Reactions
- Catalytic Cross-Coupling Reactions
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Reactions
- Tryptophan and brain disorders
- Synthesis of heterocyclic compounds
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Biological Evaluation
- Synthesis and Reactions of Organic Compounds
- Click Chemistry and Applications
- Chemical synthesis and alkaloids
- Organic Chemistry Cycloaddition Reactions
- Synthesis and Reactivity of Heterocycles
- Coordination Chemistry and Organometallics
University of Toronto
2020-2025
University Health Network
2019-2025
Krembil Research Institute
2019-2024
Deleted Institution
2024
Krembil Foundation
2020-2023
University of Missouri
2011-2023
Treventis (Canada)
2014-2023
University of Central Florida
2020-2023
Dalhousie University
2014-2022
Dupont Hospital
2021
ClpXP is a two-component mitochondrial matrix protease. The caseinolytic peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of protease P (ClpP) for proteolysis. degrades damaged respiratory chain proteins necessary cancer cell survival. Despite critical role in quality control, specific degrons, or modifications that tag substrate by human ClpXP, are still unknown. We demonstrated phosphorylated serine (pSer) targets to ClpX...
The novel coronavirus SARS-CoV-2 has become a global health concern. morbidity and mortality of the potentially lethal infection caused by this virus arise from initial viral subsequent host inflammatory response. latter may lead to excessive release pro-inflammatory cytokines, IL-6 IL-8, as well TNF-α ultimately culminating in hypercytokinemia ("cytokine storm"). To address immuno-inflammatory pathogenesis, multiple clinical trials have been proposed evaluate anti-inflammatory biologic...
Hearing impairment and mental disorders are common among residents of nursing homes for the aged; however, relationship between sensory deficit psychiatic illness has been little investigated in this population. The prevalence hearing impairment, psychiatric illness, co-morbidity was a sample 102 elderly from consecutive admissions to home aged. Examining coincidence these showed evidence an association loss paraphrenia, dysphoric states, but not cognitive impairment. results survey provide...
There is an urgent need to provide immediate and effective options for the treatment of prostate cancer (PCa) prevent progression lethal castration-resistant PCa (CRPC). The mevalonate (MVA) pathway dysregulated in PCa, statin drugs commonly prescribed hypercholesterolemia, effectively target this pathway. Statins exhibit anti-PCa activity, however resulting intracellular depletion cholesterol triggers a feedback loop that restores MVA thus diminishing efficacy contributing resistance. To...
The blood-brain barrier (BBB), composed of microvascular tight junctions and glial cell sheathing, selectively controls drug permeation into the central nervous system (CNS) by either passive diffusion or active transport. Computational techniques capable predicting molecular brain penetration are important to neurological design. A novel prediction algorithm, termed Brain Exposure Efficiency Score (BEE), is presented. BEE addresses need incorporate role trans-BBB influx efflux transporters...
New constrained heterocyclic analogues, 2a,b and 3, of Raloxifene (1) have been prepared by complementary Directed remote Metalation (DreM)/Friedel−Crafts cyclization approaches. Utilization a benzylidene-thiolactone rearrangement was successfully implemented to construct benzothiophenes 13a−c in good yields. Selective deprotection 13a 13b induced complexation followed triflation gave 18 23, thereby allowing efficient Suzuki−Miyaura cross coupling with borolane 16 give biaryls 19 24....
[reaction: see text] New anionic oxygen to alpha- and beta-vinyl carbamoyl migration reactions, 17a 26a-c --> 18 30a-c, proceed under LDA-mediated conditions leading stereoselectively highly substituted stilbenes bearing electron-donating -withdrawing substituents. Compounds are prepared by combination of efficient, directed ortho metalation, Sonogashira, Suzuki-Miyaura cross-coupling procedures.
The enzyme indoleamine 2,3 dioxygenase 1 (IDO1) catalyzes the rate-limiting step in kynurenine pathway (KP) which produces both neuroprotective and neurotoxic metabolites. Neuroinflammatory signals produced as a result of pathological conditions can increase production IDO1 boost its enzymatic capacity. KP have been implicated behavioral recovery after human traumatic brain injury (TBI), but their roles experimental models TBI are for most part unknown. We hypothesized there is an activity...
Abstract A short synthesis of the alkaloid schumanniophytine ( 1 ) starting from simple building blocks and involving directed ortho metalation (D o M), Suzuki–Miyaura cross coupling, a key ‐silicon‐induced O ‐carbamate remote anionic Fries rearrangement 3 is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Abstract Two stereocontrolled, efficient, and modular syntheses of eicosanoid lipoxin B4 (LXB 4 ) are reported. One features a stereoselective reduction followed by an asymmetric epoxidation sequence to set the vicinal diol stereocentres. The dienyne was installed via one‐pot Wittig olefination base‐mediated epoxide ring opening cascade. other approach through dihydroxylation reaction Horner‐Wadsworth‐Emmons afford common intermediate. Finally, Sonogashira coupling alkyne...
Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising therapeutic target in cancer immunotherapy and neurological disease. Thus, searching for highly active inhibitors use human cancers now focus of widespread research development efforts. In this study, we report the structure-based design 2-(5-imidazolyl)indole derivatives, series novel IDO1 which have been designed synthesized based on our previous study using N1-substituted 5-indoleimidazoles. Among these, identified one with strong...
DNA nanotechnology deals with the design of non-naturally occurring nanostructures that can be used in biotechnology, medicine, and diagnostics. In this study, we introduced a nucleic acid five-way junction (5WJ) structure for direct electrochemical analysis full-length biological RNAs. To best our knowledge, is first report on interrogation such long sequences by hybridization probes attached to solid support. A hairpin-shaped electrode-bound oligonucleotide hybridizes three adaptor...
Indoleamine 2,3-dioxygenase (IDO1) inhibition is a promising target as an Alzheimer's disease (AD) Disease-modifying therapy capable of downregulating immunopathic neuroinflammatory processes.
The objective of this study was to compare intubating conditions and neuromuscular effects using smaller doses atracurium (0.25 mg/kg 0.3 mg/kg) with the recommended dose 0.4 for intubation in children anesthetized halothane, N2O oxygen undergoing strabismus repair. All patients (10 each group) had good or excellent at 80% depression twitch height [T1 train-of-four (TOF) stimulation]. Mean times were 2.6 +/- 0.2 minutes following 0.25 2.2 mg/kg. These significantly longer (P less than 0.05)...
Insulinoma is a rare neuroendocrine tumor. It may occur sporadically or as part of the genetic tumor syndrome multiple endocrine neoplasia type 1 (MEN1). Diagnosis challenging because small size insulin producing tumors that lead to hyperinsulinemia. Advances in imaging modalities provide more accurate diagnosis primary tumors, metastasis, and functional status. allow for improved medical surgical management with new tools research tumors. Surgical excision often curative; however,...