We present the synthesis of new derivatives of natural products magnolol (1) and honokiol (2) and their evaluation as allosteric ligands for modulation of GABAA receptor activity. New derivatives were prepared via metal assisted cross-coupling reactions in two consecutive steps. Compounds were tested by means of two-electrode voltage clamp electrophysiology at the α1β2γ2 receptor subtype at low GABA concentrations. We have identified several compounds enhancing GABA induced current (IGABA) in the range similar or even higher than the lead structures. At 3μM, compound 8g enhanced IGABA by factor of 443, compared to 162 and 338 of honokiol and magnolol, respectively. Furthermore, 8g at EC10-20 features a much bigger window of separation between the α1β2γ2 and the α1β1γ2 subtypes compared to honokiol, and thus improved subtype selectivity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297288 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2014.10.091 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification and quality control of isomers in Huo-Xiang-Zheng-Qi Mixture using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry and inductive effects analysis.
J Pharm Biomed Anal
December 2024
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Institute of Collaborative Innovation in Great Health, College of Biotechnology and Food Science, Tianjin Key Laboratory of Food Biotechnology, Tianjin University of Commerce, Tianjin 300134, China. Electronic address:
Huo-Xiang-Zheng-Qi Mixture is a renowned traditional Chinese medicine formula used to treat ailments associated with dampness pathogens. This study employed ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to perform a comprehensive qualitative and quantitative analysis of the chemical compounds in Huo-Xiang-Zheng-Qi Mixture. A total of 155 compounds were identified, including 61 flavonoids and their glycosides, 36 phenylethanoid glycosides, 23 saponins, 14 coumarins, 9 organic acids, 1 amino acid, 2 nucleosides and purines, and 9 additional compounds.
View Article and Find Full Text PDFIntegrative analyses of the transcriptome and metabolome reveal comprehensive mechanisms of monolignol biosynthesis in response to bioclimatic factors in Magnolia officinalis.
BMC Plant Biol
December 2024
Beichuan Shennong Agriculture Technology Development Co., Ltd, Mianyang, 621000, China.
Background: Magnolia officinalis (M. officinalis) thrives in temperate, elevated regions, and its desiccated bark comprises medicinal monolignol. Both abiotic and biotic factors can influence the pharmacodynamic compounds of M.
View Article and Find Full Text PDFDistinct modulation of calcium-activated chloride channel TMEM16A by drug-binding sites.
Proc Natl Acad Sci U S A
December 2024
Channelopathy Research Center, Dongguk University College of Medicine, Goyang 10326, Republic of Korea.
Article Synopsis
- * Using magnolol and honokiol, researchers identified two distinct drug-binding sites on TMEM16A—one in the pore region and another nonpore pocket, each interacting differently with the channel.
- * The study highlights that out of 17 inhibitors tested, a majority acted as pore blockers, revealing the significance of the nonpore pocket and informing future drug development strategies.
Cannabinoid-like compounds found in non-cannabis plants exhibit antiseizure activity in genetic mouse models of drug-resistant epilepsy.
Epilepsia
November 2024
Discipline of Pharmacology, Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Objective: The cannabinoid cannabidiol has established antiseizure effects in drug-resistant epilepsies such as Dravet syndrome and Lennox-Gastaut syndrome. Amorfrutin 2, honokiol, and magnolol are structurally similar to cannabinoids (cannabis-like drugs) but derive from non-cannabis plants. We aimed to study the antiseizure potential of these compounds in various mouse seizure models.
View Article and Find Full Text PDFExploring Biological Targets of Magnolol and Honokiol and their Nature-Inspired Synthetic Derivatives: In Silico Identification and Experimental Validation of Estrogen Receptors.
J Nat Prod
November 2024
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy.
In this work, we describe the results of a computational investigation aimed at identifying potential biological targets of honokiol, magnolol and a series of synthetic prodrug derivatives obtained through esterification of the free hydroxyl groups. The ligand-based and structure-based analyses revealed that these compounds potentially interact with several biological targets, some of which are known while others are new. Honokiol, magnolol, and three of the newly synthesized derivatives may bind to estrogen receptors ERα and ERβ.
View Article and Find Full Text PDFWant 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!