- Selenadiazole derivatives as theranostic agents for simultaneous cancer chemo-/radiotherapy by targeting thioredoxin reductase
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The lack of early and timely diagnosis of tumors and the monitoring of their response to therapeutics have limited the successful cancer treatments. Theranostic agents are expected to realize the dual-purpose of simultaneous diagnosis and therapy for treatments of cancers. In the present study, we have examined the effects of the chemical structure of selenadiazole derivatives (SeDs) on their anticancer efficacy and radio-sensitization against clinically used X-rays. The results showed that the introduction of a nitro group (-NO2) into SeD-3 significantly enhanced the anticancer activity of SeDs. The higher lipophilicity endowed SeD-3 with higher cellular internalization ability, resulting in higher cellular uptake and anticancer efficacy. Specifically, the capacity of autofluorescence allowed the use of SeD-3 as a promising theranostic agent to directly monitor the cellular uptake, localization and biodistribution in vitro and in vivo. Interestingly, SeD-3 also significantly enhanced the sensitivity of HeLa cervical cells to X-ray-induced apoptosis by targeting the inhibition of TrxR and promoting intracellular ROS overproduction, which activated the downstream ROS-mediated signaling pathways to regulate cell apoptosis. Furthermore, SeD-3 exhibited satisfactory in vivo antitumor efficacy through the inhibition of tumor proliferation and induction of tumor cell apoptosis, and showed no toxicity to the main organs. Moreover, from the results of hematological analysis, we found that not only inhibiting the tumor growth, treatment of SeD-3 also alleviated the damage of liver, kidney and heart function of nude mice induced by HeLa xenografts. Taken together, this study demonstrates that SeDs could be further developed as an effective and safe theranostic agent for simultaneous cancer chemo-/radiotherapy.
- He, Lizhen,Ji, Shengbin,Lai, Haoqiang,Chen, Tianfeng
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Read Online
- Fluorescence imaging of selenol in HepG2 cell apoptosis induced by Na2SeO3
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A novel fluorescence probe (HB) has been designed and synthesized to image selenol in living cells and in vivo for the first time, and used to investigate the Na2SeO3 anticancer mechanism in HepG2 cells. This journal is
- Kong, Fanpeng,Hu, Bo,Gao, Yan,Xu, Kehua,Pan, Xiaohong,Huang, Fang,Zheng, Qiuling,Chen, Hao,Tang, Bo
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Read Online
- Adjusting the lipid-water distribution coefficient of iridium(iii) complexes to enhance the cellular penetration and treatment efficacy to antagonize cisplatin resistance in cervical cancer
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The effective design of metal complexes to manipulate their lipid-water distribution coefficient is an appealing strategy for improving their cellular penetration and treatment efficacy. Here, we conveniently synthesized three iridium (Ir) complexes with red fluorescence via the simple non-conjugate modification of the side arm of the ligand. Bio-evaluation revealed that upon adding non-conjugate selenium (Se) arene derivatives, the lipid-water distribution coefficient of Ir-Se was found to be suitable, not only decreasing the toxic side effects of complexes to normal cells, but also effectively improving their anticancer activity via enhancing their penetration into tumor cells. Moreover, mechanistic investigations demonstrated that Ir-Se entered R-HeLa cells through endocytosis, and triggered apoptosis via the down-regulation of the mitochondrial membrane potential and excessive production of singlet oxygen, thereby possessing a highly effective cytotoxicity to antagonize cisplatin resistance. Therefore, we developed a convenient strategy to derive functional metal complexes and revealed that the introduction of Se on the side arm of the ligand provided the complexes with the capacity to reverse multidrug resistance.
- Chen, Tianfeng,Chen, Zhen,Feng, Pengju,Hou, Liyuan,Huang, Wei,Li, Yiqun
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supporting information
p. 11556 - 11564
(2020/09/07)
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- Benzo[c][1,2,5]selenadiazole organoselenium derivatives: Synthesis, X-ray, DFT, Fukui analysis and electrochemical behavior
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Organo-selenium compounds are of a broad spectrum of potential technical applications. To date, many efforts have been devoted to develop their chemistry. In this context, two benzo[c][1,2,5]selenadiazole compounds have been synthesized and characterized by 1H NMR, 13C NMR, 19F NMR, MS and UV–Vis spectroscopic techniques. Both structures were confirmed using single-crystal X-ray diffraction analysis. Each compound crystallizes in monoclinic systems, space group P21/c forming dimeric units due to the intermolecular Se?N interactions. The dimmers are further linked by weak π···π stacking interactions between 1,2,5-selenadiazole and the six-membered aromatic rings. The electrochemical behavior of the compounds has been investigated by cyclic voltammetry. Additionally, the structural geometrical parameters, vibrational, electronic transition, Fukui analysis and redox properties of the molecules have been rationalized by DFT and TD-DFT methods using B3LYP level of theory in conjunction with 6-311G(d,p) basis set implemented in Gaussian 09 program. As a result, an excellent correlation between the electronic transitions and the electrochemical behavior was found.
- Ouahine, Halima,Hasnaoui, Ali,Hdoufane, Ismail,Idouhli, Rachid,Abouelfida, Abdessalam,Ait Ali, Mustapha,El Firdoussi, Larbi
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- A highly selective ratiometric fluorescent probe for 1,4-dithiothreitol (DTT) detection
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A highly selective ratiometric fluorescent probe, which contains an aminonaphthalimide fluorophore and a self-immolative spacer for 1,4-dithiothreitol (DTT) detection was designed and synthesized. The probe displays a 66 nm red-shift of fluorescence emiss
- Zhu, Baocun,Zhang, Xiaoling,Jia, Hongying,Li, Yamin,Liu, Haipeng,Tan, Weihong
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experimental part
p. 1650 - 1654
(2010/07/04)
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- The determination of thiols based using a probe that utilizes both an absorption red-shift and fluorescence enhancement
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A pyridylvinylene derivative containing piazselenole displayed high selectivity toward glutathione in the presence of other biorelevant analytes. The compound exhibited a 19?nm red-shift in absorption spectra and ~3-fold fluorescence intensity enhancement; in addition, it was possible to detect micromolar amounts of glutathione quantitatively using both red-shift absorbance and enhanced fluorescence. The mechanism of the reaction between the modified pyridylvinylene derivative and glutathione was confirmed using ESI-MS and absorption/fluorescence spectra.
- Zhu, Baocun,Zhang, Xiaoling,Jia, Hongying,Li, Yamin,Chen, Shutang,Zhang, Sichun
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experimental part
p. 87 - 92
(2010/11/16)
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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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- CONFORMATIONALLY RESTRICTED AROMATIC INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND METHOD
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Novel compounds are provided which are inhibitors of MTP and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases, and have the structure (I) or (IA) or (IB) including pharmaceutically acceptable salts thereof or prodrug esters thereof, wherein q is 0,1 or 2; R is H, alkyl, aryl or halogen; A is (1) a bond; (2) -O-; or (3) (i); B is: (ii) or (iii) or (iv) or (v) (wherein (a = 2, 3 or 4)) or (vi) or (vii) or (viii); and wherein L, L, R, R, R, R, R, R, R, R, R, X, (ix), (x) and (xi) are as defined herein.
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- A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors
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A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.
- Robl,Sulsky,Sun,Simpkins,Wang,Dickson Jr.,Chen,Magnin,Taunk,Slusarchyk,Biller,Lan,Connolly,Kunselman,Sabrah,Jamil,Gordon,Harrity,Wetterau
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p. 851 - 856
(2007/10/03)
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- 2,1,3-Benzoselenadiazole-5-carbaldehyde and derivatives preparations, 13C, 15N and 77Se NMR spectroscopy
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2,1,3-Benzoselenadiazole-5-carbaldehyde 5 has been prepared in 53% overall yield from 5-methyl-2,1,3-benzoselenadiazole 1, by a four-step synthesis. Compounds 1-5 and 2,1,3-benzo-selenadiazole 8 have been analysed by 1H, 13C, 15
- Morkved, Eva H.,Bjorlo, Olav,Schilf, Wojciech,Bernatowicz, Piotr
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- Photoinduced Nitro-Nitrite Rearrangement of 5-Nitroquinoxalines
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Unlike known o-nitro methyl derivatives of aromatic compounds, 6-methyl-5-nitro-, 2,3,6-trimethyl-5-nitro-, and 7-methyl-6-nitroquinoxaline and 1,6-dimethyl-5-nitroquinoxalinium perchlorate do not exhibit photochromism in aqueous-ethanolic solutions under conditions of flash photolysis with a time resolution of 50 μs. Under conditions of continuous photolysis, these 5-nitromethylquinoxaline derivatives and also 5-nitroquinoxaline undergo nitro-nitrite rearrangement to give 5-quinoxalinol derivatives with quantum yields ranging from 1 × 10-4 to 3 × 10-3; the efficiency of the photochemical reaction increases when irradiation is performed with a shorter-wave light. 6-Nitro derivatives do not form stable products of photochemical transformations under the same conditions.
- El'tsov,Selitrenikov,Rtishchev
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p. 285 - 294
(2007/10/03)
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- Formation and Rearrangement of Adducts from Benzyne and Substituted 2,1,3-Benzoselenadiazoles
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A series of 5-(1,2-benzoselenazol-3-yl)pentadienonitrile derivatives (2) has been prepared by addition of benzyne to substituted 2,1,3-benzoselenadiazoles.Some of these adducts rearrange either thermally or photochemically to give 2-(2-pyridyl)phenyl selenocyanates (7), which are reduced to 2-phenylpyridine derivatives (6) or hydrolysed to give ultimately, diselenides (9).The crystal structure of one benzyne adduct (2b) is reported and the mechanism of its rearrangement discussed.
- Bryce, Martin R.,Reynolds, Colin D.,Hanson, Peter,Vernon, John M.
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p. 607 - 613
(2007/10/02)
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