Assessing the efficacy of roots extract against third-stage larvae of and its safety profiles.

Gnathostomiasis, caused by the advanced third-stage larvae of , demands novel treatment avenues. The ethanolic root extract of has been postulated to have anthelminthic properties, suggesting its potential as an alternative remedy. In this study, roots were collected, identified, and extracted with 95 % ethanol.

LC-MS/MS analysis of didehydrostemofoline from Stemona collinsiae roots extracts in rats plasma and pharmacokinetics profile after oral administration.

Stemona collinsiae Craib., Stemonaceae, has been traditionally used as medicinal plants for insecticides, treatment of parasitic worms and various diseases in Southeast Asian countries. Its ethanolic root extract has been postulated for anthelminthic activities which has a potential for development for human gnathostomiasis drug.

Targeting Alpha7 Nicotinic Acetylcholine Receptors in Lung Cancer: Insights, Challenges, and Therapeutic Strategies.

Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is an ion-gated calcium channel that plays a significant role in various aspects of cancer pathogenesis, particularly in lung cancer. Preclinical studies have elucidated the molecular mechanism underlying α7 nAChR-associated lung cancer proliferation, chemotherapy resistance, and metastasis. Understanding and targeting this mechanism are crucial for developing therapeutic interventions aimed at disrupting α7 nAChR-mediated cancer progression and improving treatment outcomes.

Selective αβ Nicotinic Acetylcholine Receptor Ligand as a Potential Tracer for Drug Addiction.

αβ Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, αβ nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, - and -, for the development of an αβ nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction.

Inhibitory effects of Triphala on CYP isoforms and its pharmacokinetic interactions with phenacetin and midazolam in rats.

Context: Direct evidence of Triphala-drug interactions has not been provided to date.

Objective: This study was aimed to determine the effects of Triphala on cytochrome P450 (CYP) isoforms and P-glycoprotein (P-gp) and to investigate pharmacokinetic interactions of Triphala with CYP-probes in rats.

Materials And Methods: Effects of Triphala on the activities of CYP isoforms and P-gp were examined using human liver microsomes (HLMs) and Caco-2 cells, respectively.

Tiered approach for evaluation of anti-melanogenic activity of trans-N-coumaroyltyramine derivatives.

Skin hyperpigmentation is commonly treated by topical drug application. Several naturally occurring compounds exhibit attractive biological effects including anti-melanogenic activity. Chemically modified derivatives of those compounds are expected to be more efficient.

Erianthridin suppresses non-small-cell lung cancer cell metastasis through inhibition of Akt/mTOR/p70 signaling pathway.

Cancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear.

Finding of Key Interaction Mediated α3β4 and α7 Nicotinic Acetylcholine Receptor Ligand Selectivity of Quinuclidine-Triazole Chemotype.

The selective binding of six ()-quinuclidine-triazoles and their ()-enantiomers to nicotinic acetylcholine receptor (nAChR) subtypes α3β4 and α7, respectively, were analyzed by docking to provide the insight into the molecular basis for the observed stereospecific subtype discrimination. Homology modeling followed by molecular docking and molecular dynamics (MD) simulations revealed that unique amino acid residues in the complementary subunits of the nAChR subtypes are involved in subtype-specific selectivity profiles. In the complementary β4-subunit of the α3β4 nAChR binding pocket, non-conserved AspB173 through a salt bridge was found to be the key determinant for the α3β4 selectivity of the quinuclidine-triazole chemotype, explaining the 47-327-fold affinity of the ()-enantiomers as compared to their ()-enantiomer counterparts.

Relationships between amyloid levels, glucose metabolism, morphologic changes in the brain and clinical status of patients with Alzheimer's disease.

Objective: The current study was conducted to improve the understanding of relationships between regional cortical amyloid load, glucose metabolism, cortical morphology (volume), and severity of clinical symptoms in patients with AD, MCI, and age-matched controls.

Methods: To objectivize the radiological evaluation of patients with suspected AD, head-to-head multi-modality imaging studies were conducted using MRI and PET/CT with [F]FDG and [F]AV45 for visualization and quantitation of brain morphology, glucose metabolism, and amyloid levels, respectively. A total of 84 subjects was studied, including 33 patients with AD, 31 patients with MCI, and 20 age-matched healthy controls (HC).

α7-Nicotinic acetylcholine receptor antagonist QND7 suppresses non-small cell lung cancer cell proliferation and migration via inhibition of Akt/mTOR signaling.

Lung cancer, one of the most commonly found carcinoma type, has the highest mortality rate in cancer patients worldwide. Therapeutic interventions targeting to lung cancer become remaining the world significant challenge. Recently, the α7-nicotinic acetylcholine receptor (α7-nAChR) was reported to play an important role in the mechanism underlying lung cancer progression, being intriguing drug target for lung cancer therapy.

Radiosynthesis of (S)-[F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors.

Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a [F]-labelled analog of the highly affine and selective α3β4 ligand (S)-3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)quinuclidine ((S)-T1). (S)-[F]T1 was synthesized from ethynyl-4-[F]fluorobenzene ([F]5) and (S)-azidoquinuclidine by click reaction.

Varying Chirality Across Nicotinic Acetylcholine Receptor Subtypes: Selective Binding of Quinuclidine Triazole Compounds.

The novel quinuclidine -1,2,3-triazole derivatives - were designed based on the structure of . The binding studies revealed that the stereochemistry at the C3 position of the quinuclidine scaffold plays an important role in the nAChR subtype selectivity. Whereas the ()-enantiomers are selective to α7 over α4β2 (by factors of 44-225) and to a smaller degree over α3β4 (3-33), their ()-counterparts prefer α3β4 over α4β2 (62-237) as well as over α7 (5-294).

Design and Synthesis of Nicotinic Acetylcholine Receptor Antagonists and their Effect on Cognitive Impairment.

Structure modification of a lead compound (NSC13378) was accomplished in the present work by an in silico target-based design aimed at ligands acting on the nicotinic acetylcholine receptor (nAChR) for neurodegenerative diseases. A 187-compound focused library derived from the scaffold of the lead compound was screened against acetylcholine-binding proteins (AChBPs). Six compounds were identified and synthesized for binding and biological evaluations.

Cognitive improvements in a mouse model with substituted 1,2,3-triazole agonists for nicotinic acetylcholine receptors.

The α7 nicotinic acetylcholine receptor (nAChR) is a recognized drug target for dementias of aging and certain developmental disorders. Two selective and potent α7-nAChR agonists, winnowed from a list of 43 compounds characterized in a companion article (DOI: 10.1021/acschemneuro.

Selectivity optimization of substituted 1,2,3-triazoles as α7 nicotinic acetylcholine receptor agonists.

Three series of substituted anti-1,2,3-triazoles (IND, PPRD, and QND), synthesized by cycloaddition from azide and alkyne building blocks, were designed to enhance selectivity and potency profiles of a lead α7 nicotinic acetylcholine receptor (α7-nAChR) agonist, TTIn-1. Designed compounds were synthesized and screened for affinity by a radioligand binding assay. Their functional characterization as agonists and antagonists was performed by fluorescence resonance energy transfer assay using cell lines expressing transfected cDNAs, α7-nAChRs, α4β2-nAChRs, and 5HT3A receptors, and a fluorescence cell reporter.