Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (1)

Search Parameters:
Keywords = CaV3.x blockers

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
12 pages, 2681 KiB  
Article
Synthesis of Pseudellone Analogs and Characterization as Novel T-type Calcium Channel Blockers
by Dan Wang, Pratik Neupane, Lotten Ragnarsson, Robert J. Capon and Richard J. Lewis
Mar. Drugs 2018, 16(12), 475; https://doi.org/10.3390/md16120475 - 28 Nov 2018
Cited by 9 | Viewed by 4930
Abstract
T-type calcium channel (CaV3.x) blockers are receiving increasing attention as potential therapeutics for the treatment of pathophysiological disorders and diseases, including absence epilepsy, Parkinson’s disease (PD), hypertension, cardiovascular diseases, cancers, and pain. However, few clinically approved CaV3.x blockers are [...] Read more.
T-type calcium channel (CaV3.x) blockers are receiving increasing attention as potential therapeutics for the treatment of pathophysiological disorders and diseases, including absence epilepsy, Parkinson’s disease (PD), hypertension, cardiovascular diseases, cancers, and pain. However, few clinically approved CaV3.x blockers are available, and selective pharmacological tools are needed to further unravel the roles of individual CaV3.x subtypes. In this work, through an efficient synthetic route to the marine fungal product pseudellone C, we obtained bisindole alkaloid analogs of pseudellone C with a modified tryptophan moiety and identified two CaV3.2 (2, IC50 = 18.24 µM; 3, IC50 = 6.59 µM) and CaV3.3 (2, IC50 = 7.71 µM; 3, IC50 = 3.81 µM) selective blockers using a FLIPR cell-based assay measuring CaV3.x window currents. Further characterization by whole-cell patch-clamp revealed a preferential block of CaV3.1 activated current (2, IC50 = 5.60 µM; 3, IC50 = 9.91 µM), suggesting their state-dependent block is subtype specific. Full article
(This article belongs to the Special Issue Synthesis of Marine Natural Products and Analogues)
Show Figures

Graphical abstract

Back to TopTop