The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLö-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLö-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLö-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511945PMC
http://dx.doi.org/10.1021/acsmedchemlett.9b00021DOI Listing

Publication Analysis

Top Keywords

nerve agents
8
synthesis molecular
4
molecular properties
4
nerve
4
properties nerve
4
nerve agent
4
agent reactivator
4
hlö-7
4
reactivator hlö-7
4
hlö-7 dimethanesulfonate
4

Similar Publications

Background: Leprosy (Hansen's disease) is an infectious disease most common in resource-limited countries caused by the acid-fast bacilli Mycobacterium leprae and Mycobacterium lepromatosis that frequently affects the skin and peripheral nerves. Prompt diagnosis and treatment with multidrug therapy is crucial to reduce disease transmission and sequelae, which include nerve function impairment, ocular injury, and stigmatizing physical deformities. Traditional treatment of multibacillary leprosy consists of 12-24 months of multidrug therapy with dapsone, rifampin, and clofazimine.

View Article and Find Full Text PDF

Role of PCBP2 in regulating nanovesicles loaded with curcumin to mitigate neuroferroptosis in neural damage caused by heat stroke.

J Nanobiotechnology

December 2024

Key Laboratory of Special Environmental Medicine of Xinjiang, General Hospital of Xinjiang Military Command, No. 359, Youhao North Road, Urumqi, Xinjiang, China.

Objective: This study aims to elucidate the mechanisms by which nanovesicles (NVs) transport curcumin(CUR) across the blood-brain barrier to treat hypothalamic neural damage induced by heat stroke by regulating the expression of poly(c)-binding protein 2 (PCBP2).

Methods: Initially, NVs were prepared from macrophages using a continuous extrusion method. Subsequently, CUR was loaded into NVs using sonication, yielding engineered cell membrane Nanovesicles loaded with curcumin (NVs-CUR), which were characterized and subjected to in vitro and in vivo tracking analysis.

View Article and Find Full Text PDF

Botulinum neurotoxin type-A (BoNT/A), which blocks quantal acetylcholine (ACh) release at the neuromuscular junction (NMJ), has demonstrated its efficacy in the symptomatic treatment of blepharospasm. In 3.89% of patients treated for blepharospasm at Tenon Hospital, BoNT/A was no longer effective in relieving the patient's symptoms, and a partial upper myectomy of the muscle was performed.

View Article and Find Full Text PDF

Clonus is characterized by involuntary, rhythmic, oscillatory muscle contractions, typically triggered by rapid muscle stretching and is frequently associated with spastic equinovarus foot (SEVF), where it may increase risk of falls and cause discomfort, pain, and sleep disorders. We hypothesize that selective diagnostic nerve block (DNB) of the tibial nerve motor branches can help identify which muscle is primarily responsible for clonus in patients with SEVF and provide useful information for botulinum neurotoxin type A (BoNT-A) treatment. This retrospective study explored which calf muscles contributed to clonus in 91 patients with SEFV after stroke (n = 31), multiple sclerosis (n = 21), and cerebral palsy (n = 39), using selective DNB.

View Article and Find Full Text PDF

Despite their restrictions under international treaties, many chemical warfare agents (CWAs) and their toxic analogues are still used in various industrial sectors such as agriculture and chemical manufacturing. Thus, the need for sensitive and selective CWA detection remains critical. Commercially available detection methods, while accurate, are often bulky, expensive, and require specialized personnel.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!