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2 results on '"Silvestrol"'

1. Synthesis of a library of antiviral silvestrol analogues and development of novel methodologies in the field of radical chemistry

Author

Schulz, Göran and Schulz, Göran

Abstract

The first part of this dissertation deals with the design and synthesis of silvestrol and rocaglamide derivatives exhibiting antiviral properties. These two natural products, which belong to the Flavagline group, were isolated from different species of the genus Aglaia. Due to their activity as selective translation inhibitors, they found application in previous medicinal chemistry research primarily as lead structures in cancer research, but later antiviral activity against a variety of RNA viruses was also demonstrated. In the present dissertation, several strategies for the total synthesis of this class of natural products were elaborated on the basis of previous work. This allowed the preparation of a library of 40 derivatives in total. The biological testing of 27 of these compounds against hepatitis E, which was carried out by collaborators at the Ruhr University Bochum, revealed new structure-activity relationships and confirmed that the correlations established in cancer research are also applicable to the antiviral properties. In addition, it was possible to identify candidates that exhibited both higher antiviral activity and proportionally lower cytotoxicity than both natural products. The second part of this dissertation deals with the development of novel synthetic methodologies in the field of radical chemistry. Based on a MINISCI-type decarboxylation, an access to synthetically useful alkoxyamines was established. The relevance of this method was demonstrated by its application in the context of a new total synthesis approach for (±)-indatraline. Studies on the reactivity of a polymer-bound bis(azido)iodiate(I) complex, which releases the highly explosive iodine azide in a controlled manner, enabled the elucidation of several previously unknown radical mechanisms. Furthermore, several methods have been developed to generate bromine azide from stable precursors in situ for the use in organic solvents to accomplish 1,2-functionalization of alkenes and c

Published
2023

2. New Advances on Zika Virus Research.

Author

Martinez-Sobrido, Luis and Almazan Toral, Fernando

Subjects
Aedes aegypti, African-lineage, Asian lineage, Asian-lineage, Bacterial artificial chromosome, Bayesian analyses, ELISA, EQA, FSS13025, Full-length cDNA infectious clones, IgA, IgG avidity tests, MR766, NHP, NS1 protein, NS2A protein, NS5, Non-human primates, QCMD, RNA-seq, TLR7/8, Tet-inducible, ZIKV, ZIKV-associated neurologic disorders, ZIKV-host interactions, Zika, Zika virus, Zika virus (ZIKV), Ziks virus, anti-viral immunity, antiviral, antiviral compounds, antiviral responses, antivirals, apoptosis, arbovirus, assay standardization, astrocytomas, bacterial artificial chromosome, blood-retinal barrier, boolean logic-processing nucleic acid probes, cell surface receptors, chimeric viruses, clinical trials, congenital Zika syndrome, cross-reactions, cryptic promoter silencing, cytopathic effects, dengue virus, dengue viruses, detoxification and immune system responses, diagnosis, dsRNA, eIF4A, emerging arbovirus, external quality assessment, eye, fetal infection, flavivirus, flaviviruses, full-length molecular clone, gene expression, genetic variability, heme-oxygenase 1, hepatocytes, host genetic variation, host-directed antivirals, human brain glial cells, immune response, indirect immunofluorescence, infection, infectious RNA, infectious cDNA, infectious clone, innate response, insecticide resistance, isothermal nucleic acid amplification, laboratory preparedness, microRNAs, microcephaly, microglia cells, microsphere immunoassay, molecular diagnostics, monoclonal antibodies, mosquito, mosquito surveillance, mosquito-borne flavivirus, multiplex nucleic acid detection, mutagenesis, natural history, neural cells, neural progenitor cells, neuroinflammation, neurons, neuropathogenesis, nucleic acid computation, nucleic acid strand exchange, ocular, optimised, outbreak control, placenta cells, plaque reduction neutralization test, plasmid toxicity, point-of-care diagnostics, polymerase chain reaction, prM-E proteins, pregnancy, prostate, replication, replicon, reporter virus, research models and tools, reverse genetics, rhesus macaques, secondary infections, serology, sexual transmission, siRNA, silvestrol, subgenomic replicon, testes, testicular cells, testis, therapeutics, therapy, type I IFN antagonist, vaccines, validated, viral counteraction, viral evolution, viral fitness, viral genetic variation, viral pathogenesis, viral pathogenicity, viral permissiveness, viral persistence, viral replication, viral survival, virus attachment, virus like particles, zika virus
Abstract

Summary: Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders-including fetal microcephaly and Guillain-Barré syndrome in adults-have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus-host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis.

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