Both plant and mammalian cells express glucuronosyltransferases that catalyze glucuronidation of polyphenols such as flavonoids and other small molecules. Oral administration of select polyphenolic compounds leads to the accumulation of the corresponding glucuronidated metabolites at μM and sub-μM concentrations in the brain, associated with amelioration of a range of neurological symptoms. Determining the mechanisms whereby botanical extracts impact cognitive wellbeing and psychological resiliency will require investigation of the modes of action of the brain-targeted metabolites. Unfortunately, many of these compounds are not commercially available. This article describes the latest approaches for the analysis and synthesis of glucuronidated flavonoids. Synthetic schemes include both standard organic synthesis, semi-synthesis, enzymatic synthesis and use of synthetic biology utilizing heterologous enzymes in microbial platform organisms.

Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new acridinone derivatives, some of them resulting with high antiviral and trypanocidal activity. In this study new derivatives of 10-alyl-, 10-(3-methyl-2-butenyl)- and 10-(1,2-propadienyl)-9(10H)-acridinone were evaluated for their antimalarial activity against Plasmodium falciparum. To assess the selectivity, cytotoxicity was assessed in parallel against human MRC-5 cells. Inhibition of β-hematin formation was determined using a spectrophotometric assay. Mitochondrial bc(1) complexes were isolated from yeast and bovine heart cells to test acridinone inhibitory activity. This study resulted in the identification of three compounds with submicromolar efficacy against P. falciparum and without cytotoxic effects on human cellular line. One compound, IIa (1-fluoro-10-(3-methyl-2-butenyl)-9(10H)-acridinone), can be classified as hit for antimalarial drug development exhibiting IC(50) less than 0.2 μg/mL with SI greater than 100. In molecular tests, no relevant inhibitory activity was obtained for our compounds. The mechanism of acridinones antimalarial action remains unclear.

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The synthesis of substituted 2-(alkylamino)benzoic acids using the Ullmann condensation with water as the solvent and utilizing ultrasound irradiation was achieved with high yields in a short reaction time.