Biological Evaluation of New Thienopyridinium and Thienopyrimidinium Derivatives as Human Choline Kinase Inhibitors.

ABSTRACT: Due to its role in lipid biosynthesis, choline kinase α1 (CKα1) is an interesting target for the development of new antitumor agents. In this work, we present a series of 41 compounds designed based on the well-known and successful strategy of introducing thienopyridine and pyrimidine as bioisosteres of other heterocycles in active antitumor compounds. Notwithstanding the fact that some of these compounds do not show significant enzymatic inhibition, others, in contrast, feature substantially improved enzymatic and antiproliferative inhibition values. This is also confirmed by docking analysis, whereby compounds with longer linkers and thienopyrimidine cationic head have been identified as the most compelling. Among the best compounds is Ff-35, which inhibits the growth of different

SUBMITTER: Luque-Navarro PM 

PROVIDER: S-EPMC9032693 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature