Design, synthesis, and biological activity of novel para-substituted phenylamino and phenyl derivatives of northebaine as selective delta opioid receptor agonists.

The delta opioid receptor (DOR) is a promising target for developing analgesics with fewer side effects compared to mu opioid receptor (MOR) agonists. However, non-peptidyl DOR-selective agonists remain limited. Using the "message-address" concept in opioid ligand design, we designed and synthesized a series of para-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoetheno-tetrahydronorthebaines to explore their binding affinity and selectivity for DOR over MOR and kappa opioid receptor (KOR).

Structure-Activity Relationship of -Cyclopropylmethyl-7α-[-(arylcarboxamido)phenyl]-6,14-ethano-tetrahydronorthebaines as Potent and Selective Kappa Opioid Receptor Agonists.

Research on KOR agonists with reduced central nervous system side effects represents a significant area in analgesic studies. Herein, a structure-activity relationship analysis was performed for a series of -cyclopropylmethyl-7α-[-(arylcarboxamido)phenyl]-6,14-ethano-tetrahydronorthebaines. Several highly selective and potent KOR agonists have been identified.

Design, synthesis and biological evaluation of (E)-4-(2-((1H-indol-5-yl) methylene) hydrazineyl)-5,6,7,8-tetrahydropyrido [4',3':4,5] thieno[2,3-d] pyrimidine derivatives as Arf1-GEFs inhibitors for the treatment of colon cancer.

Arf1, a member of the Ras superfamily of small GTPases, plays a crucial role in lipid metabolism, tumor progression, and immune suppression, making Arf1-GEFs inhibitors attractive targets for cancer immunotherapy. However, current Arf1 inhibitors face challenges such as high toxicity and poor solubility. In this study, we report the design, synthesis, and biological evaluation of a series of (E)-4-(2-((1H-indol-5-yl) methylene) hydrazineyl)-5,6,7,8-tetrahydropyrido [4',3':4,5] thieno[2,3-d] pyrimidine derivatives, derived from the lead compound Du102.

Design, synthesis, and structure-activity relationship of 5,7- dimethylbenzo[d]thiazoles as novel Kv7.2/7.3 activators with antiepileptic effects.

The activation of neuronal Kv7 channels has emerged as an important therapeutic strategy for epilepsy due to their role in regulating neuronal excitability. Retigabine (RTG), a Kv7.2/7.

METTL1-mediated m7G modification promotes colorectal cancer metastasis via stabilization of ICAM-1.

Colorectal cancer (CRC) is one of the most common tumors worldwide, and metastatic CRC is likely to have a poor prognosis. N7-methylguanosine (m7G) is a common methylation modification that is catalyzed primarily by methyltransferase 1 (METTL1). However, the role of m7G in metastatic CRC remains unclear.

Assessment of Germplasm Improvement in Three Farmed Grass Carp Populations Based on Genetic Variability.

The assessment of genetic improvement was comprehensively analyzed using the mtDNA gene and SSR markers among three farmed grass carp populations caught in May 2024. The results of an mtDNA gene analysis in 198 individuals showed that the haplotype diversity index () and nucleotide diversity index () were 0.555 and 0.

Structure-activity relationship analysis of meta-substituted N-cyclopropylmethyl-nornepenthones with mixed KOR/MOR activities.

Substance Use Disorder (SUD) remains a significant global challenge, with current treatment options offering limited efficacy. Agonists targeting the kappa opioid receptor (KOR), especially those with additional mu opioid receptor (MOR) antagonistic activity, have shown promise in addressing SUD. In this study, a series of meta-substituted N-cyclopropylmethyl-nornepenthone derivatives were designed and synthesized, and their biological activities were assessed, leading to the identification of a KOR/MOR dual modulator, compound 10a.

Inhibition of TTX-S Na currents by a novel blocker QLS-278 for antinociception.

Genetic loss-of-function mutations of the Na1.7 channel, abundantly expressed in peripheral nociceptive neurons, cause congenital insensitivity to pain in humans, indicating that selective inhibition of the channel may lead to potential therapy for pain disorders. In this study, we investigated a novel compound, 5-chloro-N-(cyclopropylsulfonyl)-2-fluoro-4-(2-(8-(furan-2-ylmethyl)-8-azaspiro [4.

Preliminary outcomes of Neuroform Atlas stent-assisted coiling for intracranial aneurysms with small parent vessels.

Background: Although stent-assisted coiling has become a standard approach for treating intracranial aneurysms (IAs), there are limited reports on its safety and effectiveness in parent artery less than 2.5 mm in diameter. This study evaluates the feasibility, safety, and short-term outcomes of using Neuroform Atlas stent-assisted coiling for IAs with small parent vessels.

Responsive Degradable Bottlebrush Polymers Enable Drugs With Superior Efficacy and Minimal Systemic Toxicity.

Bottlebrush polymers (BBPs) have garnered significant attention as advanced drug delivery systems, capable of transporting a diverse range of therapeutic agents, including both chemical drugs and biologics. Despite their effectiveness, the empty BBP vectors post-drug release may pose long-term safety risks due to their difficult systemic clearance. Here, a responsive degradable BBP platform for cancer therapy is developed, featuring a poly(disulfide) backbone grafted with fluorine-terminated zwitterionic side chains.

Discovery of an Ortho-Substituted -Cyclopropylmethyl-7α-phenyl-6,14-ethano-tetrahydronorthebaine Derivative as a Selective and Potent Kappa Opioid Receptor Agonist with Subsided Sedative Effect.

Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of -substituted -cyclopropylmethyl-7α-phenyl-6,14-ethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, = 3.

Synthesis of easily-modified and useful dibenzo-[]azepines by palladium(II)-catalyzed cyclization/addition with a green solvent.

A novel strategy in which palladium(II)-catalyzed tandem cyclization is used to obtain N-heterocyclic architectures containing a seven-membered ring has been developed and used to synthesize a series of derivatives. The reaction uses an eco-friendly mixed solvent (water : EtOH = 2 : 1) instead of DMSO and maintains a high yield (91%). Its potential application value and reaction mechanism have also been explored.

Machine Learning-derived Multi-omics Prognostic Signature of Pyroptosis-related lncRNA with Regard to ZKSCAN2-DT and Tumor Immune Infiltration in Colorectal Cancer.

Background: Colorectal cancer (CRC) has become the most prevalent gastrointestinal malignant tumor, ranking third (10.2%) in incidence and second (9.2%) in death among all malignancies globally.

Reversal of subtype-selectivity and function by the introduction of a para-benzamidyl substituent to N-cyclopropylmethyl nornepenthone.

The discovery and development of novel μ-opioid receptor (MOR) antagonists is a significant area to combat Opioid Use Disorder (OUD). In this work, a series of para-substituted N-cyclopropylmethyl-nornepenthone derivatives were designed and synthesized and pharmacologically assayed. Compound 6a was identified as a selective MOR antagonist both in vitro and in vivo.

Design, synthesis, and biological evaluation of acyl sulfonamide derivatives with spiro cycles as Na1.7 inhibitors for antinociception.

Chronic pain, as an unmet medical need, severely impacts the quality of life. The voltage-gated sodium channel Na1.7 preferentially expressed in sensory neurons of dorsal root ganglia (DRG) serves a promising target for pain therapy.

Environmental and economic assessment of the construction, operation, and demolition of a decentralized composting facility.

Decentralized waste treatment facilities are recently highlighted for the treatment of solid waste in rural areas for being cheap, flexible, and reliable. Among them, decentralized composting is most commonly used. Many forms of decentralized composting facilities also develop and apply in developing countries, but the environmental and economical performances remain unknown.

A critical review on odor measurement and prediction.

Odor pollution has become a global environmental issue of increasing concern in recent years. Odor measurements are the basis of assessing and solving odor problems. Olfactory and chemical analysis can be used for odor and odorant measurements.

Rapid progress in neuroimaging technologies fuels central nervous system translational medicine.

Central nervous system (CNS) drug discovery suffers from high attrition rates; translational neuroscience approaches aiming to reduce these high rates include the use of brain imaging technologies. However, there is a need to better understand what methods are being used and for what diseases and purposes. Our analysis of the literature found that magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) were the neuroimaging techniques used most often in clinical trials for the most prevalent CNS diseases: Alzheimer's disease (AD), Parkinson's disease (PD), depression, and schizophrenia.

ALKBH1-mediated m A demethylation of METTL3 mRNA promotes the metastasis of colorectal cancer by downregulating SMAD7 expression.

Colorectal cancer (CRC) is one of the most common malignancies, and the main cause of death from CRC is tumor metastasis. m A RNA modification plays critical role in many biological processes. However, the role of m A modification in CRC remains unclear.