Phenylpropenoids from <i>Bupleurum fruticosum</i> as Anti-Human Rhinovirus Species A Selective Capsid Binders

The dichloromethane extract of the leaves of <i>Bupleurum fruticosum</i> was found to inhibit the replication of human rhinovirus (HRV) serotypes 14 and 39. Bioassay-guided fractionation led to the isolation of seven phenylpropenol derivatives (<b>3</b>–<b>9</b>), two polyacetylenes (<b>1</b> and <b>2</b>), and one monoterpene (<b>10</b>). Compounds <b>1</b> and <b>10</b> were identified as previously undescribed secondary metabolites after extensive 1D and 2D NMR experiments as well as high-resolution mass spectrometry. Compounds <b>2</b>, <b>4</b>, and <b>5</b> showed a selective inhibition of viral replication against HRV39 serotype, with <b>2</b> and <b>4</b> being the most active, with EC₅₀ values of 1.8 ± 0.02 and 2.4 ± 0.04 μM. Mechanism of action studies indicated that <b>4</b> behaves not only as a capsid binder, interfering with the early phases of virus replication, but also as a late-phase replication inhibitor. Docking experiments were performed to confirm the ability of the antiviral phenylpropenoids to selectively fit into the hydrophobic pocket of VP1-HRV39

Targeting Tumor Associated Carbonic Anhydrases IX and XII: Highly Isozyme Selective Coumarin and Psoralen Inhibitors

A small library of psoralen carboxylic acids and their corresponding benzenesulfonamide derivatives were designed and synthesized to evaluate their activity and selectivity toward tumor associated human carbonic anhydrase (hCA) isoforms IX and XII. Both psoralen acids and sulfonamides exhibited potent inhibition of IX and XII isozymes in the nanomolar concentration range. However, psoralen acids resulted as the most selective in comparison with the corresponding benzenesulfonamide derivatives. Our data indicate that the psoralen scaffold is a promising starting point for the design of highly selective tumor associated hCA inhibitors