Bioinspired synthesis and biological evaluation of ent-protulactones A and B.

The bioinspired and stereoselective synthesis of the furo[3,2-b] furan lactone (-)-protulactone A and the dioxabicyclo[3.3.1]nonane lactone (+)-protulactone B has been achieved based on the chiron approach. The synthesis features the utilization of a number of one-pot, sequential transformations, including a cascade reaction of reductive elimination and nucleophilic addition in a one-pot process and a one-pot sequence via cross-metathesis/acetonide deprotection/O-Michael addition/lactonization to streamline the synthesis route and avoid the tedious work of product purification. Synthetic protulactones and their analogues were evaluated for their in vitro antiproliferative activity against selected tumor cell lines (MCF-7 and Capan 2) and showed minor cytotoxicity.

Rational design of a fluorescent probe and its applications of imaging and distinguishing between exogenous and endogenous H2S in living cells.

Hydrogen sulfide (H2S), a recognized environmental pollutant, comes from a wide range of sources. For example, H2S will be produced in the process of plant protein corruption, the decomposition of domestic sewage and garbage, food processing (wine brewing), etc. and once the concentration is too high, it will cause significant damage of environment and human body. Besides H2S is an important gas signal molecule in vivo, which can be transferred through lipid membrane. Its existence level is closely related to many diseases. If we can "visually" trace the transmembrane transmission of hydrogen sulfide, it will be very helpful for the study of oxidative stress processes, cell protection, signal transduction and related diseases closely related to H2S. Although some probes can detect H2S in environment, cytoplasm and organelles, there are few reports on the release and internalization of H2S. In this work, we report a H2S fluorescence probe that can retain on the cell membrane, named PCM. The probe PCM can not only detect endogenous and exogenous H2S, but also distinguish them, this provides a general strategy for the construction of probes to detect other biomarkers. In addition, PCM has been successfully applied to the detection of endogenous and exogenous H2S in zebrafish, which has the potential to become a new chemical tool and provide help for the research of H2S-related diseases.

Croton tiglium essential oil compounds have anti-proliferative and pro-apoptotic effects in A549 lung cancer cell lines.

As a traditional Chinese medicine, Croton tiglium has the characteristics of laxative, analgesic, antibacterial and swelling. This study aimed to analyze the chemical composition of C. tiglium essential oil (CTEO) extracted from the seeds of C. tiglium and its cytotoxicity and antitumor effect in vitro. Supercritical CO2 fluid extraction technology was used to extract CTEO and the chemical constituents of the essential oil were identified by comparing the retention indices and mass spectra data taken from the NIST library with those calculated based on the C7-C40 n-alkanes standard. In vitro cytotoxicity of the CTEO was assessed against cancer cell lines (A549) and the human normal bronchial epithelial cells (HBE) using the CCK-8 assay. Proliferation was detected by colony formation experiments. Wound scratch and cell invasion assays were used to detect cell migration and invasion. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. As the results, twenty-eight compounds representing 92.39% of the total oil were identified in CTEO. The CTEO has significant antitumor activity on A549 cancer cells (IC50 48.38 µg/mL). In vitro antitumor experiments showed that CTEO treatment significantly inhibited the proliferation and migration of A549 cells, disrupted the cell cycle process, and reduced the expression levels of cyclin A, cyclin B and CDK1. CTEO can also reduce mitochondrial membrane potential, activate caspase-dependent apoptosis pathway, and finally induce apoptosis. CTEO may become an effective anti-cancer drug and will be further developed for cancer treatment.

A new phenylsulfonamide-based Golgi-targeting fluorescent probe for H2S and its bioimaging applications in living cells and zebrafish.

We have synthesized a simple Golgi-targeting H2S fluorescent probe which can detect endogenous and exogenous H2S in cells and zebrafish. In addition, this probe provides a new chemical tool for the detailed study of generation pathways of H2S under Golgi stress response.

Rational Design of a Targetable Fluorescent Probe for Visualizing H2S Production under Golgi Stress Response Elicited by Monensin.

As a eukaryotic organelle, the Golgi apparatus plays an essential role in various physiological activities such as stress response. The Golgi stress response is an important physiological process of conferring cytoprotection by regulating the synthesis and metabolism of bioactive molecules. Therefore, the development of new suitable in situ analytical techniques for monitoring related small molecular substances in the stress reaction of the Golgi apparatus is very helpful for further study of the regulatory mechanism of the Golgi apparatus. Recent studies have shown that endogenous hydrogen sulfide (H2S) also possesses crucial bioregulatory and protective performances in the stress response. Therefore, the high-fidelity in situ mapping of H2S production under the Golgi stress response plays an important role not only in revealing cytoprotection functions of H2S in the stress response but also in further understanding the regulatory mechanism of the Golgi stress response. In this work, we designed a simple Golgi-targetable H2S fluorescent probe (Gol-H2S) that responds accurately and sensitively to H2S in the Golgi apparatus of living cells and zebrafish. On the basis of its superior bioimaging performances, probe Gol-H2S was successfully applied to the in situ visualization of H2S production under the Golgi stress response elicited by monensin, a specific-Golgi stressor. The related process of the Golgi stress response was validated by stimulation and inhibition experiments. These findings fully demonstrate that H2S is an alternative biomarker of the Golgi stress response. Moreover, probe Gol-H2S can also be used as a potential tool for disclosing the detailed H2S-cytoprotection mechanisms under the regulation of the Golgi stress response in related diseases.

A novel highly sensitive fluorescent probe for bioimaging biothiols and its applications in distinguishing cancer cells from normal cells.

In recent years, targeting drugs made by physical loading or chemical bonding of drugs on small molecular carriers have shown a very wide application prospect in the field of tumor and cancer treatment. How to achieve the release of drugs in cancer cells has become the core of this research. One of the most important bases for drug localization is to use the difference of small molecular biothiol concentration between cancer cells and normal cells. Details of the changes of biothiol levels in the growth and reproduction of cancer cells are still poorly understood, and the main reason is the lack of sensitive real-time imaging tools for biothiols in cancer cells. In this work, we reasonably designed and synthesized the combination of 4-hydroxy-1,8-naphthalimide and NBD-Cl as a concise fluorescent probe HN-NBD for imaging biothiols in live cells and zebrafish. In addition, due to the advantages of HN-NBD design, it is sufficiently sensitive to biothiols, and further imaging can distinguish cancer cells from normal cells. Probe HN-NBD would be of great significance to biomedical researchers for the study of biothiol-related diseases, the screening of new anticancer drugs, and the early diagnosis and treatment of cancers.