Suramin is a polysulfonated polyaromatic symmetrical urea. It is currently used to treat African river blindness and African sleeping sickness. Suramin has also been extensively trialed recently to treat a number of other diseases, including many cancers. Here, we examine its modes of action and discuss its structure-activity relationships.

, Metal chelation, radical scavenging and inhibition of Aβ 42-fibrillation by food constituents in relation to Alzheimer's disease, Food Chemistry (2015), doi: http://dx.doi.org/10.1016/j.foodchem. 2015.11.118 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 These authors contributed equally to this work. Metal chelation, radical scavenging and inhibition of Aβ Abstract Various food constituents have been proposed as disease-modifying agents forAlzheimer's Disease (AD), due to epidemiological evidence of their beneficial effects, and for their ability to ameliorate factors linked to AD pathogenesis, namely by: chelating iron, copper and zinc; scavenging reactive oxygen species; and suppressing the fibrillation of amyloid-beta peptide (Aβ). In this study, nine different food constituents (L-ascorbic acid, caffeic acid, caffeine, curcumin, (−)-epigallocatechin gallate (EGCG), gallic acid, propyl gallate, resveratrol, and α-tocopherol) were investigated for their effects on the above factors, using metal chelation assays, antioxidant assays, and assays of Aβ 42 fibrillation. An assay method was developed using 5-Br-PAPS to examine the complexation of Zn(II) and Cu(II).EGCG, gallic acid, and curcumin were identified as a multifunctional compounds, however their poor brain uptake might limit their therapeutic effects. The antioxidants L-ascorbic acid and α-tocopherol, with better brain uptake, deserve further investigation for specifically addressing oxidative stress within the AD brain.

Structure-based virtual screening of two libraries containing 567 981 molecules was used to discover novel, selective BuChE inhibitors, which are potentially superior symptomatic treatments in late-stage Alzheimer's disease. Compound 16 was identified as a highly selective submicromolar inhibitor of BuChE (huBuChE IC50 = 0.443 μM) with high permeability in the PAMPA-BBB model. The X-ray crystal structure of huBuChE in complex with 16 revealed the atomic-level interactions and offers opportunities for further development of the series.

I want to break free: Mesoporous silica nanoparticles are functionalized with sulfasalazine (SZ; see scheme), a prodrug of 5-aminosalicylic acid (5-ASA) and sulfapyridine, to generate enzyme-responsive nanocarriers. In the presence of the colon-specific enzyme azo-reductase (orange), 5-ASA and sulfapyridine are efficiently released.

A glycosaminoglycan mimetic was attached to the surface of solid and mesoporous silica nanoparticles to create novel antiviral agents against herpes simplex type 1 and type 2 viruses. The nanoparticles act as viral entry inhibitors that appear to block viral attachment and penetration into susceptible cells.

Dysregulation of the kynurenine pathway (KP) leads to imbalances in neuroactive metabolites associated with the pathogenesis of several neurodegenerative disorders, including Huntington’s disease (HD). Inhibition of the enzyme kynurenine 3-monooxygenase (KMO) in the KP normalises these metabolic imbalances and ameliorates neurodegeneration and related phenotypes in several neurodegenerative disease models. KMO is thus a promising candidate drug target for these disorders, but known inhibitors are not brain permeable. Here, 19 new KMO inhibitors have been identified. One of these ( 1 ) is neuroprotective in a Drosophila HD model but is minimally brain penetrant in mice. The prodrug variant ( 1b ) crosses the blood–brain barrier, releases 1 in the brain, thereby lowering levels of 3-hydroxykynurenine, a toxic KP metabolite linked to neurodegeneration. Prodrug 1b will advance development of targeted therapies against multiple neurodegenerative and neuroinflammatory diseases in which KP likely plays a role, including HD, Alzheimer’s disease, and Parkinson’s disease.

The biphenyl neolignan honokiol is a neuroprotectant which has been proposed as a treatment for central nervous system disorders such as Alzheimer's disease (AD). The death of cholinergic neurons in AD is attributed to multiple factors, including accumulation and fibrillation of amyloid beta peptide (Aβ) within the brain; metal ion toxicity; and oxidative stress. In this study, we used a transgenic Caenorhabditis elegans model expressing full length Aβ as a convenient in vivo system for examining the effect of honokiol against Aβ-induced toxicity. Furthermore, honokiol was evaluated for its ability to inhibit Aβ oligomerization and fibrillation; inhibit acetylcholinesterase and butyrylcholinesterase; scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals; and chelate iron(II). Honokiol displayed activity similar to that of resveratrol and (-)-epigallocatechin gallate (EGCG) in delaying Aβ-induced paralysis in C. elegans, and it exhibited moderate-to-weak ability to inhibit Aβ on-pathway aggregation, inhibit cholinesterases, scavenge DPPH radicals, and chelate iron(II). Moreover, honokiol was found to be chemically stable relative to EGCG, which was highly unstable. Together with its good drug-likeness and brain availability, these results suggest that honokiol may be amenable to drug development and that the synthesis of honokiol analogues to optimize these properties should be considered.

Enzymvermittelte Freisetzung: Die Funktionalisierung von mesoporösen SiO2‐Nanopartikeln mit Sulfasalazin (SZ), einem Prodrug der 5‐Aminosalicylsäure (5‐ASA; siehe Schema) und von Sulfapyridin, ergibt enzymresponsive Nanotransporter. In Gegenwart des Kolon‐spezifischen Enzyms Azo‐Reduktase (orange) werden 5‐ASA und Sulfapyridin effizient freigesetzt.