Riboswitches are non-coding RNA structures located in messenger RNAs that bind endogenous ligands, such as a specific metabolite or ion, to regulate gene expression. As such, riboswitches serve as a novel, yet largely unexploited, class of emerging drug targets. Demonstrating this potential, however, has proven difficult and is restricted to structurally similar antimetabolites and semi-synthetic analogues of their cognate ligand, thus greatly restricting the chemical space and selectivity sought for such inhibitors. Here we report the discovery and characterization of ribocil, a highly selective chemical modulator of bacterial riboflavin riboswitches, which was identified in a phenotypic screen and acts as a structurally distinct synthetic mimic of the natural ligand, flavin mononucleotide, to repress riboswitch-mediated ribB gene expression and inhibit bacterial cell growth. Our findings indicate that non-coding RNA structural elements may be more broadly targeted by synthetic small molecules than previously expected.
Eleven antidiabetic traditional Chinese medicine (TCM) extracts rich in saponins were examined for their antioxidant and antiglycation activities. The antioxidant activities of these extracts were evaluated by studying the inhibition of lipid peroxidation in rat liver microsomes induced by ascorbate/Fe2+, cumine hydroperoxide (CHP) or CCl4/reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH). The antioxidant capacities were also evaluated by studying the scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical. The antiglycation activities of these extracts were evaluated by hemoglobin-delta-gluconolactone (delta-Glu) assay, bovine serum albumin (BSA)-glucose assay and N-acetyl-glycyl-lysine methyl ester (GK peptide)-ribose assay. Aralia taibaiensis outperformed other extracts in most of the assays except inhibition of early glycation products formation, where Acanthopanax senticosus showed higher activity. Aralia taibaiensis was particularly potent in inhibiting the late glycation and formation of advanced glycation end products (AGEs) on proteins. The antioxidant and antiglycation activities of most extracts were correlated with the saponin content. The results demonstrate that the antidiabetic activities of most extracts could be explained, at least in part, by their combined antioxidant and antiglycation properties.
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