No abstract

Because of the abuse of antibiotics and threats of antibiotic resistance, bacterial infection is still one of the most difficult issues to be resolved. Thus, it is of great significance to explore novel antibacterial agents. In this paper, we investigated a type of silica-coated gold–silver nanocages (Au–Ag@SiO2 NCs) as antibacterial candidates. Their intrinsic characteristics of photothermal property and sustained release of Ag ions were fully exploited for near-infrared (NIR)-induced combined anti-infective therapy. The broad-spectrum antibacterial property of the as-prepared Au–Ag@SiO2 NCs was confirmed in vitro against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). In addition, Au–Ag@SiO2 NCs exhibit effective treatment of the S. aureus biofilm with the assistance of NIR irradiation. More importantly, we assessed the in vivo antibacterial efficacy of Au–Ag@SiO2 NCs against S. aureus, which demonstrated sustainably enhanced therapeutic effects on a rat model with wound infection.

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

No abstract

Eight drimane sesquiterpenoids including (-)-drimenol and (+)albicanol were synthesized from (+)-sclareolide and evaluated for their antifungal activities. Three compounds, (-)-drimenol, (+)-albicanol, and (1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydronaphthalene-1carbaldehyde (4) showed strong activity against C. albicans. (-)-Drimenol, the strongest inhibitor of the three, (at concentrations of 8-64 µg/ml, causing 100% death of various fungi), acts not only against C. albicans in a fungicidal manner, but also inhibits other fungi such as Aspergillus, Cryptococcus, Pneumocystis, Blastomyces, Saksenaea and fluconazole resistant strains of C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. auris. These observations suggest that drimenol is a broad-spectrum antifungal agent. At a high concentration (100 μg/ml) drimenol caused rupture of the fungal cell wall/membrane. In a nematode model of C. albicans infection, drimenol rescued the worms from C. albicans-mediated death, indicating drimenol is tolerable and bioactive in metazoans. Genome-wide fitness profiling assays of both S. cerevisiae (nonessential homozygous and essential heterozygous) and C. albicans (Tn-insertion mutants) collections revealed putative genes and pathways affected by drimenol. Using a C. albicans mutant spot assay, the Crk1 kinase associated gene products, Ret2, Cdc37, and orf19.759, orf19.1672, and orf19.4382 were revealed to be involved in drimenol's mechanism of action. The three orfs identified in this study are novel and appear to be linked with Crk1 function. Further, computational modeling results suggest possible modifications of the structure of drimenol, including the A ring, for improving the antifungal activity.

A phytochemical investigation of the EtOH extract from the rhizomes and roots of Smilax scobinicaulis resulted in the isolation of a new isospirostanol-type steroidal saponin, namely (25 R)-5α-spirostan-3β,6β-diol 3-O-β-D-glucopyranosyl-(1 → 4)-[α-L-arabinopyranosyl-(1 → 6)]-β-D-glucopyranoside (1), along with four known steroidal saponins (2-5). The structures of these compounds were determined by 1D- and 2D-NMR spectroscopic analysis, FABMS and HR-ESI-MS as well as chemical degradation. The isolated saponins were evaluated for their in vitro cytotoxicity against A549, LAC and Hela human cancer cell lines, which demonstrated that only compound 1 possessed significant cytotoxic activity with IC₅₀ values of 3.70, 5.70 and 3.64 µM, respectively.

No abstract

Brassinosteroids (BRs) are a class of plant steroid hormones that play indispensable roles in cell elongation, division and plant development. To date, the numerous synthesis of BRs analogs and structure-activity relationship investigations have clearly revealed the key substituent groups relevant to the steroidal activity of BRs. However, due to the limited chemical space studied, the efforts for alternative non-steroidal compounds have produced no remarkable results. To identify potentially non-steroidal BR mimics in this study, vital interacting pharmacophore features were extracted starting from several complex structures of BRs that bound with the receptor Brassinosteroid-Insentive 1 (BRI1) and co-receptor BRI1-associated kinase 1 (BAK1), which were characterized and merged into one comprehensive pharmacophore model. In silico screening of a commercial compound database was carried out by combing pharmacophore modeling, molecular docking and visual analysis. Finally, six non-steroidal molecules were identified and subjected to the in vivo radish hypocotyl elongation assay. As a positive control, the hypocotyls elongation for the naturally most active BR brassinolide (BL) is 152 ± 3% at 100 nM. Moreover, two candidates (4 and 6) show good BRs-like activity with the hypocotyls elongation of 143 ± 1% and 128 ± 3% at the same dose, respectively. Most remarkably, compounds 4 and 6, which have different structures, are predicted to share similar binding modes and proven to exhibit potential BRs-like activity. The two compounds obtained could be valuable leads for the development of BRs-like plant growth regulators.