In this study a microwave-assisted method was applied for the synthesis of novel 9-(substituted indolyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione derivatives. The structures of the compounds were confirmed by spectral methods including X-ray studies and elemental analysis. The Emax and pD2 values of the compounds and pinacidil were determined on noradrenaline precontracted tissues of isolated strips of rabbit gastric fundus smooth muscle. The obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on the strips. The efficacy of compound 9 was higher than pinacidil. Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. Methyl substituents on the acridine backbone and bromine atom on the indole ring led to more active compounds.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.ejmech.2014.01.059 | DOI Listing |
Sci Robot
October 2024
Program in Molecular Medicine, Hospital for Sick Children, Toronto, ON, Canada.
Arrhythmogenic cardiomyopathy (ACM) is a leading cause of sudden cardiac death among young adults. Aberrant gap junction remodeling has been linked to disease-causative mutations in plakophilin-2 (). Although gap junctions are a key therapeutic target, measurement of gap junction function in preclinical disease models is technically challenging.
View Article and Find Full Text PDFFront Pharmacol
June 2023
Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, United States.
K channels have diverse roles, including regulation of insulin secretion and blood flow, and protection against biological stress responses and are excellent therapeutic targets. Different subclasses of K channels exist in various tissue types due to the unique assemblies of specific pore-forming (Kir6.x) and accessory (SURx) subunits.
View Article and Find Full Text PDFExp Eye Res
July 2023
Institute of Ophthalmology, University College London (UCL), London, UK; Imperial College of Science and Technology, St. Mary's Campus, London, UK; Eye-ACP Duke-National University of Singapore Medical School, Singapore; Singapore Eye Research Institute (SERI), Singapore; Department of Pharmacy Sciences, Creighton University, Omaha, NE, USA; Department of Pharmacology and Neuroscience, University of North Texas Health Sciences Center, Fort Worth, Texas, USA; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA; Ophthalmology Innovation Center, Santen Inc USA, Emeryville, CA, USA. Electronic address:
A multitude of pharmacological compounds have been shown to lower and control intraocular pressure (IOP) in numerous species of animals and human subjects after topical ocular dosing or via other routes of administration. Most researchers have been interested in finding drug candidates that exhibit a relatively long duration of action from a chronic therapeutic use perspective, for example to treat ocular hypertension (OHT), primary open-angle glaucoma and even normotensive glaucoma. However, it is equally important to seek and characterize treatment modalities which offer a rapid onset of action to help provide fast relief from quickly rising IOP that occurs in certain eye diseases.
View Article and Find Full Text PDFNutrients
July 2021
Division of Food Science, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
Seeds of industrial hemp ( L.) contain a large amount of protein (26.3%), dietary fiber (27.
View Article and Find Full Text PDFPflugers Arch
December 2020
Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsin-Lung Road, Sec. 3, Taipei, Taiwan.
Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!