Affiliation:
1. Latvian Institute of Organic Synthesis Aizkraukles 21 1006 Riga Latvia
2. Faculty of Pharmacy Rīga Stradiņš University Konsula 21 1007 Riga Latvia
3. Institute of Technology of Organic Chemistry Faculty of Materials Science and Applied Chemistry Riga Technical University P. Valdena iela 3 1048 Riga Latvia
Abstract
AbstractWe aimed to design and synthesize 3‐methylenechroman‐2‐one derivatives and test their potency as TrxR1 inhibitors. A convenient and easy‐to‐handle synthetic approach to 3‐methylenechroman‐2‐ones was developed. The in vitro inhibitory activity towards recombinant TrxR1 was determined for the obtained compounds. The most potent representatives exhibited submicromolar TrxR1 inhibition activity (IC50 varied from 0.29 μM to 10.2 μM). Structure‐activity relationship analysis indicates the beneficial role of the substituent at the position C‐6 of the core of chroman‐2‐one, where the derivatives containing halogen are the most active among the scope of compounds obtained. The most potent TrxR1 inhibitor of the series was further examined in in vitro cell‐based assays to assess cytotoxic effects on various cancer cell lines, and to evaluate their influence on cell apoptosis.
Subject
Organic Chemistry,General Pharmacology, Toxicology and Pharmaceutics,Molecular Medicine,Drug Discovery,Biochemistry,Pharmacology