Xiao Yun Chen

Two-Photon Fluorescent Probes of Biological Zn(II) Derived from 7-Hydroxyquinoline

A new fluorescent probe for monitoring Zn(2+) was synthesized based on the structure of 7-hydroxyquinoline. Compared with 8-substituted quinolines, the new probe exhibited higher selectivity for Zn(2+) over Cd(2+). Its fluorescence enhancement (14-fold) and nanomolar range sensitivity (K(d) = 0.117 nM) were favorable toward biological applications. Experiments also showed that a cell-permeable derivative of the new probe was potentially useful for two-photon imaging in living cells.

Benzimidazole Derivatives: Selective Fluorescent Chemosensors for the Picogram Detection of Picric Acid

1,3,5-Tri(1H-benzo[d]imidazol-2-yl)benzene derivatives, as a new kind of fluorescent chemosensor for the detection of nitroaromatic explosives, are designed and synthesized by simple N-hydrocarbylation. Among 16 obtained compounds, compound 4g has the best capability for detection of picric acid (PA), having good selectivity and high sensitivity. The detection of PA with 4g solution-coated paper strips at the picogram level is developed. A simple, portable, and low-cost method is provided for detecting PA in solution and contact mode.

Copper-Catalyzed N-Alkynylations of Sulfoximines with Bromoacetylenes

N-Alkynylated sulfoximines have been obtained by copper-catalyzed cross-coupling reactions starting from NH-sulfoximines and bromoacetylenes in moderate to good yields. The reaction conditions are mild, and the substrate scope is wide.

Syntheses and biological activities of sulfoximine-based acyclic triaryl olefins.

Sulfoximine-based acyclic triaryl olefins 8 and 9 have been prepared and initial studies have been performed to determine their biological profiles. In contrast to their sulfonyl-substituted analog 2 sulfoximines 8 and 9 show low COX inhibitory activity. All compounds affect the estrogen receptors. While sulfone 2 interacts exclusively with ER β, sulfoximines 8 and 9 reveal almost equal blocking potencies for both estrogen receptors, ER α and ER β. In the tested series, triaryl olefin 9a shows the highest inhibitory activities with 91% and 80%, respectively (at 10 μM).

Photoregulation of thrombin aptamer activity using Bhc caging strategy.

Thrombin aptamer was attempted to cage with Bhc (6-bromo-7-hydroxycoumarin-4-ylmethyl) group for controlling its specific affinity to target molecular through photolysis. By multiple-caging strategy, aptamer could be rendered biologically inert and partially restored with subsequently illumination. This provides a convenient method for photoregulating aptamer activity with exact spatiotemporal resolution.

Palladium/Copper‐Cocatalyzed Oxidative Amidobrominations of Alkenes

In the presence of LiBr, a palladium/copper combination catalyzes dehydrogenative amidobrominations of acrylates with NH-sulfoximines, leading to N-vinylated products by dual NH/CH coupling, followed by oxidative enamide bromination. Mechanistically, the domino process is proposed to involve palladium(II) species as key intermediates. First synthetic applications of the products have been demonstrated.

Anti-glioma Activity of Dapsone and Its Enhancement by Synthetic Chemical Modification

The sulfone dapsone is an old antibiotic used for the treatment of mycobacterial and protozoal infections. We postulated before that dapsone might possess biological activity exceeding its anti-infectious properties and that it could potentially be repurposed for the treatment of glioma. To test this hypothesis, we treated established and primary cultured glioma cells with dapsone or several dapsone analogues which we previously synthesized (D2–D5) and determined effects on proliferation, anchorage-independent growth and migration. While dapsone and its synthetic analogues D2–D5 displayed only modest anti-proliferative activity, important neoplastic features such as anchorage-independent growth, clonogenic survival and directed migration were significantly inhibited by dapsone treatment. Moreover, dapsone analogues D3, D4 and D5 yielded even enhanced anti-glioma activity against different pro-neoplastic features. Overall these data suggest that dapsone provides activity against glioma which can be further enhanced by molecular modifications. These compounds could potentially serve as a therapeutic adjunct to the treatment of gliomas in a repurposing approach.

Synthesis of a Sulfonimidamide-Based Analog of Tasisulam and Its Biological Evaluation in the Melanoma Cell Lines SKMel23 and A375

Tasisulam is a promising antitumor agent with complex pharmacology, which is used as an antiproliferative agent in patients with metastatic melanoma and other solid tumors. Phase 2 melanoma studies showed promising results but had to be stopped because of insufficient tasisulam clearance leading to toxic side effects. To reduce the negative effects of tasisulam, we synthesized a novel sulfonimidamide-based analog to evaluate its antiproliferative effects in comparison to the original compound by performing a cell proliferation assay in melanoma cell lines SKMel23 and A375. The results revealed that the analog had inhibitory effects on the proliferation comparable to tasisulam in both investigated cell lines. These results could contribute to a reduced toxicity of tasisulam and lead to further clinical trials in metastatic melanoma.

Contents Vol. 29, 2016

N. Ahmad, Madison, Wis. C. Antoniou, Athens J.M. Baron, Aachen E. Benfeldt, Roskilde E. Berardesca, Rome K. De Paepe, Brussels P. Elsner, Jena A. Farkas, Zurich N. Garcia Bartels, Berlin M.W. Greaves, London R.H. Guy, Bath S. Hedtrich, Berlin E.M. Jackson, Bonney Lake, Wash. H. Kandárová, Ashland, Mass. L. Kemeny, Szeged J. Kresken, Viersen J. Krutmann, Düsseldorf B. Lange-Asschenfeldt, Klagenfurt am Wörthersee R. Neubert, Halle T. Ruzicka, Munich M. Schäfer-Korting, Berlin M. Schmuth, Innsbruck S. Seidenari, Modena P.W. Wertz, Iowa City, Iowa J. Wohlrab, Halle L. Zastrow, Monaco Journal of Pharmacological and Biophysical Research