Design, synthesis, and evaluation of antitumor activity of novel C-6 sulfhydryl-substituted and 20-substituted derivatives of celastrol.

Celastrol has been identified as a potential candidate for anticancer drug development. In this study, 28 novel celastrol derivatives with C-6 sulfhydryl substitution and 20-substitution were designed and synthesized, and their antiproliferative activity against human cancer cells and non-malignant human cells was evaluated, with cisplatin and celastrol being used as controls. The results showed that most of the derivatives had enhanced in vitro anticancer activity compared to the parent compound celastrol. Specifically, derivative 2f demonstrated the most potent inhibitory potential and selectivity against HOS with an IC50 value of 0.82 µM. Our study provides new insights into the structure-activity relationship of celastrol and suggests that compound 2f may be a promising drug candidate for the treatment of osteosarcoma.

Sequencing, assembly, annotation, and gene expression: novel insights into browning-resistant Luffa cylindrica.

Luffa is a kind of melon crop widely cultivated in temperate regions worldwide. Browning is one of the serious factors affecting the quality of Luffa. Therefore, the molecular mechanism of Luffa browning is of great significance to study. However, the molecular diversity of Luffa cultivars with different browning-resistant abilities has not been well elucidated. In our study, we used high-throughput sequencing to determine the transcriptome of two Luffa cylindrica cultivars '2D-2' and '35D-7'. A total of 115,099 unigenes were clustered, of which 22,607 were differentially expression genes (DEGs). Of these DEGs, 65 encoding polyphenol oxidase, peroxidase, or ascorbate peroxidase were further analyzed. The quantitative real-time PCR (RT-qPCR) data indicated that the expression levels of the LcPPO gene (Accession No.: Cluster-21832.13892) was significantly higher in '35D-7' compared with that in '2D-2'. Several POD genes (Accession No.: Cluster-21832.19847, Cluster-21832.30619 and Cluster-48491.2) were also upregulated. Analysis of the plantTFDB database indicated that some transcription factors such as WRKY gene family may also participate in the regulation of Luffa browning. The results indicated that the divergence of genes expression related to enzymatic reaction may lead to the different browning resistances of Luffa. Our study will provide a theoretical basis for breeding of browning-resistant Luffa.

Enantioselective Total Synthesis of (-)-Pavidolide B.

The enantioselective synthesis of (-)-pavidolide B (1) was achieved in a linear sequence of 10 steps. The key steps are (a) an enantioselective organocatalytic cyclopropanation; (b) a radical-based cascade annulation for the regio- and diastereo-selective synthesis of the highly functionalized lactone 3 bearing the characteristic tricyclic core and seven contiguous stereocenters;

[Evaluation of the rapid trehalose test for the identification of the Candida glabrata].

OBJECTIVE: To explore a rapid and cost-effective method for identification of Candida glabrata through the comparison of two different methods, using molecular methods of sequencing as gold standard. METHODS: From our clinic, 200 strains of suspected Candida glabrata were collected during the last 3 years and selected after incubation in CHROMagar Candida medium for 48 h. By comparing the results of the CHROMagar Candida medium, the identification of the rapid trehalose test for different kinds of strains were analyzed under incubation in the tubes for 3 h, 6 h, and 24 h at 37 °C and 42 °C, respectively. All the strains were identified to species level by methods of sequencing. The optimal time and temperature of the trehalose test for the identification of Candida glabrata were assessed. Two different methods, CHROMagar Candida medium and the rapid trehalose test, in identification of Candida glabrata were compared. RESULTS: In all the 200 strains, Candida glabrata ferment trehalose with 3 h incubation under 42 °C were the optimal time and temperature for fermenting trehalose. The accuracy, sensitivity, and specificity of the rapid trehalose test were 99.00% (198/200), 98.66% (147/149) and 100.00% (51/51). The accuracy rate of CHROMagar Candida medium was 79.50% (159/200), the sensitivity and specificity were only 89.93% (134/149) and 49.02% (25/51), however, compared with the domestic current popular methods, the rapid trehalose test had better time efficiency ratio. CONCLUSION: The evaluation results suggest that the rapid trehalose test has advantages in terms of operational convenience and low cost, and the results can be obtained in 3 h. Therefore, it has application value in clinical laboratory.

One-pot stepwise approach to ß-enaminoketoesters through "masked" 1,3-aza-dipoles.

t-BuOK-mediated rearrangement of 1,3-ketoesters with 2-(azidomethyl) aromatics in a two-step, one-pot telescoped sequence affords ß-enaminoketoesters in moderate to good yields. A novel pathway is proposed in which the umpolung of the azide is achieved from electrophilicity to nucleophilicity via deprotonation and undergoes nucleophilic attack onto the 1,3-ketoester.