A5069898931- Hepatitis B Virus Studies
- Hepatitis C virus research
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Liver Disease Diagnosis and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Telomeres, Telomerase, and Senescence
- Adipose Tissue and Metabolism
- Phytochemicals and Antioxidant Activities
- Lipid metabolism and disorders
- S100 Proteins and Annexins
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Single-cell and spatial transcriptomics
- Genomics, phytochemicals, and oxidative stress
- Lipid metabolism and biosynthesis
- Cancer, Lipids, and Metabolism
- Chemical Synthesis and Analysis
- Asymmetric Hydrogenation and Catalysis
- Sirtuins and Resveratrol in Medicine
National Institutes of Health
2015-2021
National Institute of Diabetes and Digestive and Kidney Diseases
2017-2021
University of Oxford
2019-2020
National Center for Advancing Translational Sciences
2015
Oxidative stress (OS) in non-alcoholic fatty liver disease (NAFLD) promotes injury and inflammation. Treatment with vitamin E (α-tocopherol, αT), a lipid-soluble antioxidant, improves but also decreases steatosis, thought to be upstream of OS, through an unknown mechanism. To elucidate the mechanism, we combined mechanistic human trial interrogating pathways intrahepatic triglyceride (IHTG) accumulation vitro experiments. 50% NAFLD patients (n = 20) treated αT (200-800 IU/d) for 24 weeks had...
Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and vivo activity against hepatitis C virus. Here, describe structure-activity relationship (SAR) efforts resulted the optimization of novel derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM HCV infection, cytotoxicity selectivity indices above 2000, showed improved pharmacokinetic properties. The optimized molecules can serve lead...
Cellular senescence has been shown to be sufficient for the development of multiple age-related pathologies. Senescent cells adopt a secretory phenotype (the SASP) which comprises large number pro-inflammatory cytokines, chemokines and proteases. The SASP itself is thought causative in many pathologies diseases, there growing interest developing seno-modifying agents that can suppress SASP. However, order identify new agents, it necessary conduct moderate high throughput screening with...
The unusual α-amino, β-hydroxy acid MeBmt is a key structural feature of cyclosporin A, an important naturally occurring immunosuppressant and antiviral agent. We present convergent synthesis which relies on new aspects dynamic kinetic resolution (DKR) to establish simultaneously the chirality at C(2) C(3). also show that this route applicable other derivatives.
Hepatitis C virus (HCV) is a small, single-stranded, positive-sense RNA that infects more than an estimated 70 million people worldwide. Untreated, persistent HCV infection often results in chronic hepatitis, cirrhosis, or liver failure, with progression to hepatocellular carcinoma. Current anti-HCV regimens comprising direct acting antivirals (DAAs) can provide curative treatment; however, due high costs there remains need for effective, shorter-duration, and affordable treatments....
The majority of FDA-approved HCV therapeutics target the viral replicative machinery. An automated high-throughput phenotypic screen identified several small molecules as potent inhibitors hepatitis C virus replication. Here, we disclose discovery and optimization a 4-aminopiperidine (4AP) scaffold targeting assembly stages life cycle. original screening hit (1) demonstrates efficacy in HCVcc assay but does not show potency prior to or during Colocalization infectivity studies indicate that...