A5018876062- interferon and immune responses
- Respiratory viral infections research
- Influenza Virus Research Studies
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- PARP inhibition in cancer therapy
- Chemical Synthesis and Analysis
- Trypanosoma species research and implications
- Cell death mechanisms and regulation
- Toxin Mechanisms and Immunotoxins
- Parasites and Host Interactions
- Research on Leishmaniasis Studies
Sapienza University of Rome
2020-2021
LSD1 is a lysine demethylase highly involved in initiation and development of cancer. To design effective covalent inhibitors, strategy to fill its large catalytic cleft by designing tranylcypromine (TCP) analogs decorated with long, hindered substituents. We prepared three series TCP analogs, carrying aroyl- arylacetylamino (1 a-h), Z-amino acylamino (2 a-o), or double-substituted benzamide (3 a-n) residues at the C4 C3 position phenyl ring. Further fragments obtained chemical manipulation...
Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/β-catenin pathway-dependent solid tumors. Previously, we reported the 2-mercaptoquinazolin-4-one MC2050 a micromolar PARP1 inhibitor. Here show how resolution of X-ray structure complex with MC2050, combined computational investigation structural differences between TNKSs and PARP1/2 active sites, provided rationale for structure-based drug design campaign that limited synthetic effort led to discovery...
Influenza viruses represent a major threat to human health and are responsible for seasonal epidemics, along with pandemics. Currently, few therapeutic options available, most drugs being at risk of the insurgence resistant strains. Hence, novel approaches targeting less explored pathways urgently needed. In this work, we assayed library nitrobenzoxadiazole derivatives against influenza virus A/Puerto Rico/8/34 H1N1 (PR8) strain. We identified three promising 4-thioether substituted...