Synthesis and antitumor evaluation of (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole as potential PI3K/AKT/mTOR signaling pathway inhibitors.

In an attempt to search for new natural product-based antitumor agents, a series of novel (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary bioassay showed that compounds 5r and 5s presented certain inhibitory activity against cancer cells, weak cytotoxic activity against normal cells, and inhibitory activity against PI3K/AKT/mTOR signaling pathway. The binding modes and the binding site interactions between the active compounds and the target proteins were predicted preliminarily by the molecular docking method.

Nanoengineered, magnetically guided drug delivery for tumors: A developmental study.

Fighting against tumors is an ongoing challenge in both medicinal and clinical applications. In recent years, chemotherapy, along with surgery, has significantly improved the situation to prolong life expectancy. Theoretically, and regardless of dosage, we now have drugs that are strong enough to eliminate most tumors. However, due to uncontrollable drug distribution in the body, it is difficult to increase treatment efficiency by simply increasing dosages. For this reason, the need for a drug delivery system that can release "bombs" at the target organ or tissue as precisely as possible has elicited the interest of researchers. In our work, we design and construct a silica-based nanocomposite to meet the above demand. The novel nanocomposite drug carrier can be guided to target tumors or tissue by a magnetic field, since it is constructed with superparamagnetic Fe3O4 as the core. The Fe3O4 core is clad in a mesoporous silica molecular sieve MCM-41 (represented as MS, in this article), since this MS has enormous ordered hexagonal caves providing sufficient space to hold the drug molecules. To modify the magnetically guided carriers so that they become both magnetically guided and light-responsive, benzophenone hydrazone is coupled into the molecular sieve tunnel. When a certain wavelength of light is imposed on the gating molecules, C=N double bonds vibrate and swing, causing the cavity that holds the drug molecules to change size and open the tunnels. Hence, the nanocomposite has the ability to release loaded drugs with light irradiation. The structure, loading abilities, and the size of the nanocomposite are inspected with a scanning electron microscope, a transmission electron microscope, thermogravimetry analysis, N2 adsorption/desorption, and dynamic light scattering The biocompatibility and in vitro drug molecule controlled release are tested with an SMMC-7721 cell line.

Towards recyclable optical nitrite sensing composite structures: Design, synthesis, characterization and sensing performance.

Two site-specific nanocomposite samples were designed and prepared for nitrite sensing. A core-shell structure was applied in them, using Fe3O4 nanoparticles as core, silica molecular sieve MCM-41 as shell and two rhodamine derivatives as chemosensor, respectively. These two composite samples and their core-shell structure were investigated by electron microscopy images, N2 adsorption/desorption, magnetic property, IR spectra and thermogravimetric analysis. Nitrite sensing performance of these two composite samples was evaluated with their emission quenching. Limit of detection was determined as 1.1µM. Further analysis indicated that our chemosensors followed a static sensing mechanism based on an additive reaction between NO+ and chemosensors. These two composite samples showed recyclability after being quenched by nitrite.

An inhibitor of chondroitin sulfate proteoglycan synthesis promotes central nervous system remyelination.

Remyelination is the generation of new myelin sheaths after injury facilitated by processes of differentiating oligodendrocyte precursor cells (OPCs). Although this repair phenomenon occurs in lesions of multiple sclerosis patients, many lesions fail to completely remyelinate. A number of factors have been identified that contribute to remyelination failure, including the upregulated chondroitin sulfate proteoglycans (CSPGs) that comprise part of the astrogliotic scar. We show that in vitro, OPCs have dramatically reduced process outgrowth in the presence of CSPGs, and a medication library that includes a number of recently reported OPC differentiation drugs failed to rescue this inhibitory phenotype on CSPGs. We introduce a novel CSPG synthesis inhibitor to reduce CSPG content and find rescued process outgrowth from OPCs in vitro and accelerated remyelination following focal demyelination in mice. Preventing CSPG deposition into the lesion microenvironment may be a useful strategy to promote repair in multiple sclerosis and other neurological disorders.

On a magnetic-luminescent nanocomposite for oxygen sensing application: Construction, characterization and sensing performance.

This paper was devoted to the construction of a magnetic-luminescence nanocomposite for oxygen sensing application, where superparamagnetic Fe3O4 and silica molecular sieve MCM-41 were chosen as the inner core and the outer shell, respectively. A Ru(II) complex was grafted into MCM-41 shell through a coupling ligand N1-(5H-cyclopenta[1,2-b:5,4-b']dipyridin-5-ylidene)benzene-1,4-diamine (denoted as Dafo-Ph-NH2). The final composite was analyzed by electron microscope images, XRD, IR spectra, thermogravimetry and N2 adsorption/desorption. Oxygen sensing performance of this composite was evaluated. Sensitivity of 5.8 (the ratio of emission intensity in pure N2 to that in pure O2) and response time of 16s were obtained with good photostability.

Efficient regioselective O3-monodesilylation by hydrochloric acid in cyclodextrins.

An efficient O3-monodesilylation method has been developed for the derivatization of per-3-O-silylated cyclodextrin (CD) derivatives. Using hydrochloric acid as a reagent, the O3-monodesilylation was found to be regioselective, mild, practical and general as it can be applied to all α-, ß- and γ-CDs. The advantage of the methodology is that the acid-catalyzed O3-desilylation can be carried out in a stepwise manner so that different types of functional groups can be introduced to a CD molecule at different stage of the O3-desilylations. This makes the current methodology flexible and versatile. This current methodology constitutes one of the few methodologies available for the regioselective modification of CDs at the secondary face.