Silychristin: Skeletal Alterations and Biological Activities

Silychristin is the second most abundant flavonolignan (after silybin) present in the fruits of <i>Silybum marianum</i>. A group of compounds containing silychristin (<b>3</b>) and its derivatives such as 2,3-dehydrosilychristin (<b>4</b>), 2,3-dehydroanhydrosilychristin (<b>5</b>), anhydrosilychristin (<b>6</b>), silyhermin (<b>7</b>), and isosilychristin (<b>8</b>) were studied. Physicochemical data of these compounds acquired at high resolution were compared. The absolute configuration of silyhermin (<b>7</b>) was proposed to be identical to silychristin A (<b>3a</b>) in ring D (10<i>R</i>,11<i>S</i>). The preparation of 2,3-dehydrosilychristin (<b>4</b>) was optimized. The Folin–Ciocalteau reduction and DPPH and ABTS radical scavenging assays revealed silychristin and its analogues to be powerful antioxidants, which were found to be more potent than silybin and 2,3-dehydrosilybin. Compounds <b>4</b>–<b>6</b> exhibited inhibition of microsomal lipoperoxidation (IC₅₀ 4–6 μM). Moreover, compounds <b>4</b>–<b>8</b> were found to be almost noncytotoxic for 10 human cell lines of different histogenetic origins. On the basis of these results, compounds <b>3</b>–<b>6</b> are likely responsible for most of the antioxidant properties of silymarin attributed traditionally to silybin (silibinin)

Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents

The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report the synthesis of novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO II display excellent activities against Gram-positive and -negative bacteria, including pathogens and multiresistant strains. We describe their mechanism of action–plasmatic membrane pore-forming activity selective for bacteria. Importantly, LPPO II neither damage nor cross the eukaryotic plasmatic membrane at their bactericidal concentrations. Further, we demonstrate LPPO II have low propensity for resistance development, likely due to their rapid membrane-targeting mode of action. Finally, we reveal that LPPO II are not toxic to either eukaryotic cells or model animals when administered orally or topically. Collectively, these results suggest that LPPO II are highly promising compounds for development into pharmaceuticals