Discovery & Structure-Activity Relationship Studies of the Inhibitors of RNA Methyltransferase

Abstract

RNA methylation, which is a reversible post translational modification, occurs frequently in eukaryotic messenger RNAs (mRNAs) and has been reported to play an important role in biological processes. There are various components involved in RNA methylation, among which RNA methyltransferase serves to attach methyl group to RNA. Recent studies have shown that dysregulation of RNA methyltransferase has oncogenic effects in several types of cancer, suggesting that it may be a target for cancer treatment. In this study, we report the development of compounds as new RNA methyltransferase inhibitors that suppress enzymatic activity. In order to obtain a lead compound of the RNA methyltransferase inhibitor, compound screening was performed by enzyme-based assay and one hit compound with enzyme inhibitory effect was selected. To further increase the inhibitory activity of the hit compound, a structure-activity relationship (SAR) study was explored. We examined the effect of carbon chain length and the positional effect of alkyl chains. Subsequently, the inhibitory activity was confirmed by enzyme-based assay. Therefore, this study suggests the possibility of derivatives as a new RNA methyltransferase inhibitor.