Glycybridins A–K, Bioactive Phenolic Compounds from <i>Glycyrrhiza glabra</i>

In an attempt to discover bioactive agents from the herbal medicine <i>Glycyrrhiza glabra</i> (widely known as licorice), 11 new phenolic compounds, glycybridins A–K (<b>1</b>–<b>11</b>), along with 47 known phenolics (<b>12</b>–<b>58</b>) were isolated. Their structures were elucidated on the basis of extensive NMR and MS analyses as well as experimental and computed ECD data. According to the clinical therapeutic effects of licorice, enzyme or cell-based bioactivity screenings of <b>1</b>–<b>58</b> were conducted. A number of compounds significantly activate Nrf2, inhibit tyrosinase or PTP1B, inhibit LPS-induced NO production and NF-κB transcription, and inhibit the proliferation of human cancer cells (HepG2, SW480, A549, MCF7). Glycybridin D (<b>4</b>) showed moderate cytotoxic activities against the four cancer cell lines, with IC₅₀ values ranging from 4.6 to 6.6 μM. Further studies indicated that <b>4</b> (10 mg/kg, ip) decreased tumor mass by 39.7% on an A549 human lung carcinoma xenograft mice model, but showed little toxicity

Antcamphins A–L, Ergostanoids from <i>Antrodia camphorata</i>

Twelve ergostanoids, named antcamphins A–L (<b>1</b>–<b>12</b>), together with 20 known triterpenoids, were isolated from fruiting bodies of the medicinal fungus <i>Antrodia camphorata</i>. Compounds <b>1</b> and <b>2</b> represent the first examples of norergostanes isolated from <i>A. camphorata</i>, and compounds <b>3</b> and <b>4</b> are the first pair of <i>cis</i>–<i>trans</i> isomers of ergostane-type triterpenoids containing an aldehyde group. Compounds <b>5</b>–<b>12</b> are four pairs of C-25 epimers. The structures of <b>1</b>–<b>12</b> were elucidated on the basis of extensive spectroscopic data analysis including NMR and HRESIMS. Particularly, the absolute configurations at C-25 for <b>5</b>–<b>12</b> were determined by the modified Mosher’s method. These triterpenoids exhibited weak cytotoxic activities against MDA-MB-231 breast cancer cells and A549 lung cancer cells, but did not inhibit the growth of normal cells in the sulforhodamine B assay

Density Functional Theory Calculations in Stereochemical Determination of Terpecurcumins J–W, Cytotoxic Terpene-Conjugated Curcuminoids from Curcuma longa L.

Fourteen novel terpene-conjugated curcuminoids, terpecurcumins J–W (<b>1</b>–<b>14</b>), have been isolated from the rhizomes of Curcuma longa L. Among them, terpecurcumins J–Q and V represent four unprecedented skeletons featuring an unusual core of hydro­benzannulated­[6,6]-spiroketal (<b>1</b> and <b>2</b>), bicyclo[2.2.2]­octene (<b>3</b>–<b>7</b>), bicyclo[3.1.3]­octene (<b>8</b>), and spiroepoxide (<b>13</b>), respectively. The structures of compounds <b>1</b>–<b>14</b> were elucidated by extensive spectroscopic analysis, and their absolute configurations were established by electronic circular dichroism, vibrational circular dichroism, and ¹³C NMR spectroscopic data analysis, together with density functional theory calculations. The structure and configuration of <b>1</b> was further confirmed by single-crystal X-ray diffraction (Cu Kα). The biogenetic pathways of <b>1</b>–<b>14</b> were proposed, involving Michael addition, condensation, Diels–Alder cyclo­addition, and electrophilic substitution reactions. Terpecurcumins showed more potent cytotoxic activities than curcumin and ar-/β-turmerone. Among them, terpecurcumin Q (<b>8</b>) exhibited IC₅₀ of 3.9 μM against MCF-7 human breast cancer cells, and mitochondria-mediated apoptosis played an important role in the overall growth inhibition. Finally, LC/MS/MS quantitative analysis of five representative terpecurcumins indicated these novel compounds were present in C. longa at parts per million level

Terpecurcumins A–I from the Rhizomes of <i>Curcuma longa</i>: Absolute Configuration and Cytotoxic Activity

Terpecurcumins A–I (<b>1</b>–<b>9</b>), together with three known analogues (<b>10</b>–<b>12</b>), were isolated from the rhizomes of <i>Curcuma longa</i> (turmeric). They were derived from the hybridization of curcuminoids and bisabolanes. The structures and absolute configurations of <b>1</b>–<b>9</b> were elucidated on the basis of extensive spectroscopic data analysis, including NMR and electronic circular dichroism spectra. The configuration of <b>10</b> was further confirmed by X-ray crystallography. A plausible biogenetic relationship for <b>1</b>–<b>12</b> is proposed. Compounds <b>4</b>, <b>6</b>, <b>7</b>, <b>10</b>, and <b>11</b> showed higher cytotoxic activities (IC₅₀, 10.3–19.4 μM) than curcumin (IC₅₀, 31.3–49.2 μM) against human cancer cell lines (A549, HepG2, and MDA-MB-231)

Density Functional Theory Calculations in Stereochemical Determination of Terpecurcumins J–W, Cytotoxic Terpene-Conjugated Curcuminoids from Curcuma longa L.

Fourteen novel terpene-conjugated curcuminoids, terpecurcumins J–W (<b>1</b>–<b>14</b>), have been isolated from the rhizomes of Curcuma longa L. Among them, terpecurcumins J–Q and V represent four unprecedented skeletons featuring an unusual core of hydro­benzannulated­[6,6]-spiroketal (<b>1</b> and <b>2</b>), bicyclo[2.2.2]­octene (<b>3</b>–<b>7</b>), bicyclo[3.1.3]­octene (<b>8</b>), and spiroepoxide (<b>13</b>), respectively. The structures of compounds <b>1</b>–<b>14</b> were elucidated by extensive spectroscopic analysis, and their absolute configurations were established by electronic circular dichroism, vibrational circular dichroism, and ¹³C NMR spectroscopic data analysis, together with density functional theory calculations. The structure and configuration of <b>1</b> was further confirmed by single-crystal X-ray diffraction (Cu Kα). The biogenetic pathways of <b>1</b>–<b>14</b> were proposed, involving Michael addition, condensation, Diels–Alder cyclo­addition, and electrophilic substitution reactions. Terpecurcumins showed more potent cytotoxic activities than curcumin and ar-/β-turmerone. Among them, terpecurcumin Q (<b>8</b>) exhibited IC₅₀ of 3.9 μM against MCF-7 human breast cancer cells, and mitochondria-mediated apoptosis played an important role in the overall growth inhibition. Finally, LC/MS/MS quantitative analysis of five representative terpecurcumins indicated these novel compounds were present in C. longa at parts per million level

Uralsaponins M–Y, Antiviral Triterpenoid Saponins from the Roots of <i>Glycyrrhiza uralensis</i>

Thirteen new oleanane-type triterpenoid saponins, uralsaponins M–Y (<b>1</b>–<b>13</b>), and 15 known analogues (<b>14</b>–<b>28</b>) were isolated from the roots of <i>Glycyrrhiza uralensis</i> Fisch. The structures of <b>1</b>–<b>13</b> were identified on the basis of extensive NMR and MS data analyses. The sugar residues were identified by gas chromatography and ion chromatography coupled with pulsed amperometric detection after hydrolysis. Saponins containing a galacturonic acid (<b>1</b>–<b>3</b>) or xylose (<b>5</b>) residue are reported from <i>Glycyrrhiza</i> species for the first time. Compounds <b>1</b>, <b>7</b>, <b>8</b>, and <b>24</b> exhibited good inhibitory activities against the influenza virus A/WSN/33 (H1N1) in MDCK cells with IC₅₀ values of 48.0, 42.7, 39.6, and 49.1 μM, respectively, versus 45.6 μM of the positive control oseltamivir phosphate. In addition, compounds <b>24</b> and <b>28</b> showed anti-HIV activities with IC₅₀ values of 29.5 and 41.7 μM, respectively

Bioactive Constituents of <i>Glycyrrhiza uralensis</i> (Licorice): Discovery of the Effective Components of a Traditional Herbal Medicine

Traditional herbal medicines have been reported to possess significant bioactivities. In this investigation, a combined strategy using both phytochemical and biological approaches was conducted to discern the effective components of licorice, a widely used herbal medicine. Altogether, 122 compounds (<b>1</b>–<b>122</b>), including six new structures (<b>1</b>–<b>6</b>), were isolated and identified from the roots and rhizomes of <i>Glycyrrhiza uralensis</i> (licorice). These compounds were then screened using 11 cell- and enzyme-based bioassay methods, including Nrf2 activation, NO inhibition, NF-κB inhibition, H1N1 virus inhibition, cytotoxicity for cancer cells (HepG2, SW480, A549, MCF7), PTP1B inhibition, tyrosinase inhibition, and AChE inhibition. A number of bioactive compounds, particularly isoprenylated phenolics, were found for the first time. Echinatin (<b>7</b>), a potent Nrf2 activator, was selected as an example for further biological work. It attenuated CCl₄-induced liver damage in mice (5 or 10 mg/kg, ip) and thus is responsible, at least in part, for the hepatoprotective activity of licorice