A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor.

ABSTRACT: Chloroethylagelastatin A (CEAA) is an analogue of agelastatin A (AA), a natural alkaloid derived from a marine sponge. It is under development for therapeutic use against brain tumors as it has excellent central nervous system (CNS) penetration and pre-clinical therapeutic activity against brain tumors. Recently, AA was shown to inhibit protein synthesis by binding to the ribosomal A-site. In this study, we developed a novel virtual screening platform to perform a comprehensive screening of various AA analogues showing that AA analogues with proven therapeutic activity including CEAA have significant ribosomal binding capacity whereas therapeutically inactive analogues show poor ribosomal binding and revealing structural fingerprint features essential for drug-ribosome interactions. In par

SUBMITTER: Caulfield TR 

PROVIDER: S-EPMC7599554 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature