Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20( S )-Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents

Twelve novel 20-sulfonylamidine derivatives (9a–9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Compound 9a demonstrated better cytotoxicity against MDR cells compared with that of 1 and 3. Mechanistically, 9a induced significant DNA damage by selectively inhibiting Topoisomerase (Topo) I and activating the ATM/Chk related DNA damage-response pathway. In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg. Notably, 9a at 300 mg/kg (i.p.) showed no overt toxicity in contrast to 1 (LD50 56.2 mg/kg, i.p.) and 3 (LD50 177.5 mg/kg, i.p.). Intact 9a inhibited Topo I activity in a cell-free assay in a manner similar to that of 1, confirming that 9a is a new class of Topo I inhibitor. 20-Sulfonylamidine 1-derivative 9a merits development as an anticancer clinical trial candidate

Application of Lanthanide Shift Reagent to the 1H-NMR Assignments of Acridone Alkaloids

This study investigates the application of the paramagnetic shift reagent tris(dipivaloylmethanato)-europium(III) in NMR spectral studies of permethoxyacridone alkaloids (1–3) and pyranoacridone alkaloids (4–6). The induced chemical shifts (∆δ) of all protons were observed for the same molecule, and were compared to deduce the positions resulting from the distance nearby the Eu(dpm)3. Assignment of the H-2, H-4 and H-8 of polysubstituted acridones could be distinguished based on the least-squares method of lanthanide-induced shifts plotted against the mole ratios of Eu(dpm)3 to the substrate. The developed method is not only potentially useful for determining the planar structures of polysubstituted compounds, such as acridones, anthraquinones, xanthones, flavonoids, and phenanthrenes, but also applicable for their stereochemistry

Antifatigue and Antioxidant Activity of Alcoholic Extract from Saussurea involucrata

Fatigue is a noticeable and highly prevalent symptom in tense, industriously, and economically affluent modern society. Therefore, new antifatigue agents to smooth the fatigue feature are an energetic topic. The total ethanol extract (ESI) of Saussurea involucrata Kar et Kir., known as Tian-Shan snow lotus, was evaluated for antifatigue activity in ICR mice with mice forced swimming test and the determination of the contents of blood lactic acid and serum urea nitrogen. ESI (0.05, 0.15, 0.25 g/kg) was administered orally to mice for 4 weeks. The average swimming times to exhaustion of the ESI-treated ICR mice (0.15, 0.25 g/kg) were prolonged by 132% and 180% (p<0.001) with a lessening of fatigue compared with that of the control group. Analysis of biochemical parameters showed that levels of serum urea nitrogen and blood lactic acid of experimental groups were also decreased significantly (p<0.001) compared with that of the control group. The antioxidant activity of ESI was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay and the hydrogen peroxide-induced luminol chemiluminescence assay and the results indicated that ESI exerts DPPH scavenging ability and reducing power. These results provide scientific evidence that S. involucrata may have been potential as an antifatigue agent

Bioassay-guided purification of sesquiterpenoids from the fruiting bodies of Fomitopsis pinicola and their anti-inflammatory activity.

Twelve undescribed sesquiterpenoids, fomitopins A-L (1-12), were isolated via bioassay-guided purification from the bracket fungus Fomitopsis pinicola (Sw.) P. Karst, and this fungus have been reported to exhibit anti-microbial and anti-inflammatory activities. The structures of 1-12 were elucidated by spectroscopic and spectrometric analyses and their absolute configurations were further confirmed by ECD simulations. Ten isolated compounds were evaluated for their anti-inflammatory potential and compound 11 exhibited the most significant inhibition of superoxide anion generation and elastase release with IC50 values of 0.81 ± 0.15 and 0.74 ± 0.12 μM. These newly purified sesquiterpenoids could be potential candidates for further anti-inflammatory studies

A feasible and practical 1H NMR analytical method for the quality control and quantification of bioactive principles in Lycii Fructus

Lycii Fructus, a solanaceous drug, is widely used as functional foods and in Traditional Chinese Medicine. Samples collected from different regions of China have been found to be not identical in chemical compositions which might affect the biological activities. Although many chromatographic and spectrometric methods have been reported to determine the concentration of betaine and other bioactive amino acids, disturbance resulted from other polar substances with low UV-absorbance and expensive mass facilities reduced the applicability of these techniques. In the present study, the strong cation exchange solid phase extraction procedure incorporated with 1H NMR was successfully developed as a rapid and reliable method that can simultaneously determine betaine, citric acid, threonine, alanine, and proline in various Lycii Fructus. In addition, ERETIC 2 method based on PULCON principle was also applied and compared with conventional method. This feasible and practical method offers a very powerful tool for the quality control of commercial Lycii Fructus from different sources. Keywords: ERETIC 2, Betaine, 1H NMR, Lycii Fructus, PULCO

Beneficial effects of the burdock ferment liquid on diabetic disorders in STZ-induced diabetic rats

Abstract: The present study was undertaken to characterize the effects of the burdock (Arctium lappa L.) ferment liquid (BFL) on diabetic disorders employing streptozotocin-induced diabetic rats (STZ-diabetic rats) as a type-1 diabetic model. There was a tendency towards a reduction in hypercholesterolemia after oral administration of BFL in diabetic rats for 2 consecutive weeks. BFL with abundant inulin was capable of alleviating significantly the hypertriglyceridemia and hyperglycemia. Diabetic-dependent alterations in serum creatinine concentrations, blood urea nitrogen and creatinine clearance were ameliorated after 2-week treatment with BFL in a dose-dependent manner. Additionally, BFL with polyphenolic components was able to scavenge 1,1-diphenyl-2-picrylhydrazyl radical as well as to attenuate the oxidative stress, evidenced by the reduction of hyperactivity in antioxidants including superoxide diamutase and glutathione peroxidase in plasma of diabetic rats. Thus, BFL has the ability to decrease the hyperlipidemia and hyperglycemia, and alleviate the hyperglycemia-associated oxidative stress in STZdiabetic rats

Chemical Constituents and Anti-inflammatory Principles from the Fruits of <i>Forsythia suspensa</i>

Fifty compounds were isolated from the fruits of <i>Forsythia suspensa</i>, including 13 new compounds characterized as eight new diterpenoids (<b>1</b>–<b>8</b>), three new lignans (<b>9</b>–<b>11</b>), a new iridoid (<b>12</b>), and a new triterpenoid (<b>13</b>). Their structures were established on the basis of spectroscopic and spectrometric analysis. Most of the isolated compounds were examined for their anti-inflammatory activity in vitro. The results showed that several compounds displayed significant inhibition of fMLP/CB-induced superoxide anion generation and elastase release, with IC₅₀ values ranging from 0.6 ± 0.1 to 8.6 ± 0.8 μg/mL and from 0.8 ± 0.3 to 7.3 ± 1.1 μg/mL, respectively

γ- and δ‑Lactams from the Leaves of <i>Clausena lansium</i>

Eight new clausenamides, including three γ-lactams (<b>1</b>–<b>3</b>), four δ-lactams (<b>4</b>–<b>7</b>), and an amide (<b>8</b>), and seven known lactams, including compounds <b>9</b>–<b>11</b>, which were purified from natural sources for the first time, were characterized from the leaves of <i>Clausena lansium</i>. Their structures were elucidated using spectroscopic methods, and the absolute configurations were determined using electronic circular dichroism and single-crystal X-ray diffraction analyses with Cu Kα radiation. Compound <b>2</b> (50 μM) protected 22.24% of cortical neurons against Aβ_25–35-induced cell death

Postfermented Tea Extract Potently Alleviates Glucose Metabolism Disorders In Vitro and In Vivo

This study explores the efficacy of postfermented tea extract in mitigating type 2 diabetes mellitus (T2DM), a condition characterized by insulin resistance and reduced insulin secretion, leading to significant healthcare challenges and increased mortality. We investigated the impact of postfermented tea extract on glucose metabolism in TNF-α-stimulated C2C12 cells and its therapeutic potential in streptozotocin-induced diabetic rats. Our results showed that postfermented tea extract enhances glucose uptake in a dose-dependent manner, indicated by increased 2-NBDG absorption. This effect is linked to the activation of IRS, PI3K, and Akt pathways and the upregulation of GLUT4 expression in C2C12 cells, suggesting a reduction in insulin resistance. Additionally, the oral administration of the extract significantly lowered plasma glucose levels in diabetic rats during glucose tolerance tests. These findings underscore the potential of postfermented tea extract as a functional food ingredient for T2DM prevention, highlighting its role in ameliorating glucose metabolism disorders