- Benzoselenadiazole-based responsive long-lifetime photoluminescent probes for protein kinases
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Benzoselenadiazole-containing inhibitors of protein kinases were constructed and their capability to emit phosphorescence in the kinase-bound state was established. Labelling of the inhibitors with a red fluorescent dye led to sensitive responsive photoluminescent probes for protein kinase CK2 that emitted red light with a long (microsecond-scale) decay time upon excitation of the probes with a pulse of near-UV light. This journal is the Partner Organisations 2014.
- Ekambaram, Ramesh,Enkvist, Erki,Manoharan, Ganesh Babu,Ugandi, Mihkel,Kasari, Marje,Viht, Kaido,Knapp, Stefan,Issinger, Olaf-Georg,Uri, Asko
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- Activity enhancement of selective antitumoral selenodiazoles formulated with poloxamine micelles
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Selenium (Se) incorporated into organic frameworks has demonstrated anticancer activity against several cancer types. One of the drawbacks of most of these constructs is their poor solubility and bioavailability, which can be overcome with the use of suitable nanocarriers. We have synthesized a series of 5-substituted amide selenodiazoles, based on the parent structure of ebselen, an organoselenium drug with proven cytoprotective activity, and solubilized them in polymeric micelles of poloxamines, poly(ethylene oxide)-poly(propylene oxide) X-shaped tetrablock-copolymers. Scattering methods (SANS and DLS) were employed to characterize the micellar nanocarriers. MTT biological evaluation highlights the selectivity of the Se-compounds towards cancer cells, with MCF-7 standing as the most responsive line. The alkylation of the heterocycle with a 12-carbon hydrophobic tail displays the highest activity, showing a 100-fold increase with respect to ebselen. This compound also exhibits the greatest increase in solubility in poloxamine micelles, overall resulting in a one-fold increase in activity with respect to the non-formulated form, making it a hit compound for further optimization.
- úriz, Amaia,Sanmartín, Carmen,Plano, Daniel,de Melo Barbosa, Raquel,Dreiss, Cécile A.,González-Gaitano, Gustavo
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- Microwave-Assisted Syntheses of Benzimidazole-Containing Selenadiazole Derivatives That Induce Cell-Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway
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The use of selenium-containing heterocyclic compounds as potent cancer chemopreventive and chemotherapeutic agents has been well documented by a large number of clinical studies. In this study we developed a new approach to synthesize four benzimidazole-containing selenadiazole derivatives (BSeDs). The method uses a combination of peptide coupling reagents and microwave irradiation. This strategy features milder reaction conditions, higher yields, and shorter reaction times. The synthetic BSeDs were identified as potent antiproliferative agents against the human MCF-7 and MDA-MB-231 breast cancer cell lines. Compounds 1 b (5-(6-methyl-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), 1 c (5-(6-chloro-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), and 1 d (5-(6-bromo-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole) were found to show greater cytotoxicity against the triple-negative breast cancer cell line MDA-MB-231 than MCF-7, and to exhibit dose-dependent inhibition of cell migration, in which a significant decrease in the zone of cell monolayer wound closure was observed relative to untreated controls. Our results demonstrate that BSeDs can cause cell-cycle arrest and apoptosis in MDA-MB-231 cells by inducing DNA damage, inhibiting protein kinase B (AKT), and activating mitogen-activated protein kinase (MAPK) family members through the overproduction of reactive oxygen species (ROS). Taken together, the results of this study provide a facile microwave-assisted strategy for the synthesis of selenium-containing organic compounds that exhibit a high level of anticancer efficacy.
- Liang, Yuanwei,Zhou, Yangliang,Deng, Shulin,Chen, Tianfeng
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- Electrodeposited Organic-Inorganic Nanohybrid as Robust Bifunctional Electrocatalyst for Water Splitting
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Rational engineering of novel nanohybrid materials for sustainable and efficient energy conversion has gained extensive research interest. Cross-linked nanosheets of organic-inorganic nanohybrids (BSeF/Ni(OH)2) were fabricated by one-step reductive electrosynthesis and subsequently applied for electrocatalytic water electrolysis. The organic-inorganic nanohybrids consist of benzo[2,1,3]selenadiazole-5-carbonyl phenylalanine (BSeF) cross-linked with nickel ions (Ni-BSeF) and nickel hydroxides (Ni(OH)2), which provide abundant active sites and feasible charge transfer at the electrocatalytic interface. The resulting electrodeposited nanohybrid BSeF/Ni(OH)2 exhibits bifunctional electrocatalytic performance with 240 and 401 mV of overpotential at +100 and -100 mA cm-2 for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. The BSeF/Ni(OH)2 offers a longer electrocatalytic activity of 20 h for OER and HER at applied high current densities of +400 and -200 mA cm-2. Coupled with the high OER and HER activity, the two-electrode-based system of BSeF/Ni(OH)2 shows a low cell potential of 1.54 V at 10 mA cm-2. The electrocatalytic performance of Ni-BSeF and Ni(OH)2-based organic-inorganic nanohybrids provides an efficient way to develop a nanohybrid-based catalytic system for energy conversion.
- Das, Apurba K.,Jadhav, Rohit G.,Krivoshapkin, Pavel V.,Singh, Devraj
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- Substitution Effect on 2-(Oxazolinyl)-phenols and 1,2,5-Chalcogenadiazole -Annulated Derivatives: Emission-Color-Tunable, Minimalistic Excited-State Intramolecular Proton Transfer (ESIPT)-Based Luminophores
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Minimalistic 2-(oxazolinyl)-phenols substituted with different electron-donating and -withdrawing groups as well as 1,2,5-chalcogenadiazole-annulated derivatives thereof were synthesized and investigated in regard to their emission behavior in solution as well as in the solid state. Depending on the nature of the incorporated substituent and its position, emission efficiencies were increased or diminished, resulting in AIE or ACQ characteristics. Single-crystal analysis revealed J- and H-type packing motifs and a so-far undescribed isolation of ESIPT-based fluorophores in the keto form.
- G?bel, Dominik,Rusch, Pascal,Duvinage, Daniel,Stauch, Tim,Bigall, Nadja-C.,Nachtsheim, Boris J.
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supporting information
p. 14333 - 14355
(2021/10/20)
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- Novel selenadiazole derivatives as selective antitumor and radical scavenging agents
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Twenty-seven novel benzo[c][1,2,5]selenadiazole-5-carboxylic acid (BSCA) derivatives were designed and synthesized. Anti-proliferative activity of these structures was tested in vitro against a panel of five human cancer cell lines, including prostate (PC-3), colon (HT-29), leukemia (CCRF-CEM), lung (HTB-54) and breast (MCF-7). Four compounds (5, 6, 7 and 19) showed potent inhibitory activity with GI50 values below 10 μM in at least one of the cancer cell lines. The selectivity of these compounds was further examined in two non-malignant cell lines derived from breast (184B5) and lung (BEAS-2B). Compound 7 exhibited promising anti-proliferative activity (GI50 = 3.7 μM) in MCF-7 cells, together with high selectivity index (SI > 27.1). The induction of cell death by compound 7 was independent of the apoptotic process and it did not affect cell cycle progression either. Likewise, radical scavenging properties of the new selenadiazole derivatives were confirmed by testing their ability to scavenge DPPH radicals. Four compounds (1, 2, 8 and 9) showed potent radical scavenging activity, compound 9 being the most effective. Overall, while compound 7 was identified as the most cell growth inhibitory agent and selectively toxic to cancer cells, compound 9 proved to be the most potent antioxidant among the selenadiazole derivatives synthesized. This series of compounds can serve as an excellent scaffold to achieve new and potent antioxidant compounds useful for several diseases, i.e. cancer, neurodegenerative, heart diseases and leishmaniasis, considering the high radical scavenging activity and low toxicity showed by most of the compounds.
- Ruberte, Ana Carolina,Plano, Daniel,Encío, Ignacio,Aydillo, Carlos,Sharma, Arun K.,Sanmartín, Carmen
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- Organic selenium salt and preparation method thereof
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The invention discloses an organic selenium salt as well as a preparation method and application thereof. The molecular structural formula of the organic selenium salt is as follows: (as described inthe specification), wherein R is Na, K, Li, Mg, Ca or organic base, n represents chemical valence, - represents negative charge, and + represents positive charge. The organic selenium salt provided bythe invention has good water solubility, can be directly dissolved in water, and has a good application prospect.
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Paragraph 0021; 0025; 0029; 0030; 0037; 0038; 0045; 0046
(2019/01/08)
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- Enhancement of cell uptake and antitumor activity of selenadiazole derivatives through interaction and delivery by serum albumin
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Serum albumin is an important carrier in the transport of endogenous and exogenous substances across cell membranes. Small molecule drugs could bind to serum albumin to various extents after intravenous injection, which may affect the bioavailability, metabolism, pharmacological and toxicological potency. Organic selenium (Se) compounds exhibit favorable biocompatibility and low toxicity that attracts increased attention from researchers. Herein, a series of selenadiazole derivatives (4a-e) have been synthesized and their cytotoxicity towards various kinds of cells were evaluated. The results suggested that isopropyl benzo[c][1,2,5]selenadiazole-5-carboxylate (4d) exhibited a broad inhibition spectrum on the proliferation of tested cancer cells, with a relatively higher anticancer activity than other derivatives. We found that the differences in their anticancer activities were attributed to the various binding abilities of the Se compounds toward BSA. The bimolecular quenching constant (Kq), apparent quenching constant (KSV), effective binding constant (KA) and binding site number (n) were obtained through fluorescence quenching calculations, which indicated that all compounds could efficiently bind to BSA molecules and the fluorescence quenching mechanism was mainly a static quenching procedure. Moreover, serum albumin was found to interact with selenadiazole derivatives (4a-e), thus promoting the cellular uptake and anticancer activity of the Se compounds. Taken together, this study demonstrated that the synthetic selenadiazole derivatives exhibited high anticancer activity and cellular uptake through delivery by human serum.
- Deng, Shulin,Zeng, Delong,Luo, Yi,Zhao, Jianfu,Li, Xiaoling,Zhao, Zhennan,Chen, Tianfeng
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p. 16721 - 16729
(2017/03/24)
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- Synthesis and in vitro anticancer activities of some selenadiazole derivatives
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A novel series of fourteen substituted selenadiazoles has been synthesized and the compounds tested for their in vitro antiproliferative and cytotoxic activities. The tests were carried out against leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54), and breast (MCF-7) cancer cells. In order to assess the selectivity of the compounds under investigation the assays were also carried out on two non-tumoral lines - one mammary (184B5) and one bronchial epithelium (BEAS-2B) cell line. Assay-based antiproliferative activity studies revealed that seven derivatives (2a, 2c, 2e, 2f, 2g, 3a, and 3b) exhibited good activity against MCF-7 cells: for instance, 2c and 2f inhibited cell growth with nanomolar GI50 values. Compound 2f had a better antitumoral profile than vinorelbine and paclitaxel, two drugs that are used as first-line treatments in advanced, recurrent, and/or metastatic cancer. In the other cell lines the compounds showed moderate activity or were inactive - with the exception of 2a, which was also found to have antiproliferative activity. Modulation of the cell cycle and apoptotic effects of active compounds were further evaluated in MCF-7 cells. Of these, 6-bromo[1,2,5]selenadiazolo[3,4-b] pyridine (2a) was the most active, with an apoptogenic effect 3.9 times higher than that of camptothecin, which was used as a positive control. Compound 2a also provoked cell cycle arrest with a significant decrease in the G 0/G1 phase cell population and an increase in S and G 2/M cells, thus suggesting mitotic arrest prior to metaphase. A novel series of fourteen substituted selenadiazoles has been synthesized and the compounds tested for their in vitro antiproliferative and cytotoxic activities against several cancer cells and in order to assess the selectivity of the compounds on two non-tumoral lines. Modulation of cell cycle and apoptotic effects of active compounds were further evaluated. Copyright
- Plano, Daniel,Moreno, Esther,Font, Maria,Encio, Ignacio,Palop, Juan Antonio,Sanmartin, Carmen
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experimental part
p. 680 - 691
(2011/09/15)
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