| 1. |
- Fridén-Saxin, Maria, 1979, et al.
(author)
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Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:16, s. 7104-7113
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Journal article (peer-reviewed)abstract
- A series of substituted chromone/chroman-4-one derivatives has been synthesized and evaluated as novel inhibitors of SIRT2, an enzyme involved in aging-related diseases, e.g., neurodegenerative disorders. The analogues were efficiently synthesized in a one-step procedure including a base-mediated aldol condensation using microwave irradiation. The most potent compounds, with inhibitory concentrations in the low micromolar range, were substituted in the 2-, 6-, and 8-positions. Larger, electron-withdrawing substituents in the 6- and 8-positions were favorable. The most potent inhibitor of SIRT2 was 6,8-dibromo-2-pentylchroman-4-one with an IC50 of 1.5 mu M. The synthesized compounds show high selectivity toward SIRT2 over SIRT1 and SIRT3 and represent an important starting point for the development of novel SIRT2 inhibitors.
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| 4. |
- Meinander, K., et al.
(author)
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Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activity
- 2013
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In: Medchemcomm. - : Royal Society of Chemistry (RSC). - 2040-2503 .- 2040-2511. ; 4:3, s. 549-553
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Journal article (peer-reviewed)abstract
- Pseudopeptides based on the kallikrein-related peptidase 3 (KLK3) activating bicyclic peptide “C-4” comprising hydrocarbon-based disulphide bridge mimetics have been synthesized. After investigating different synthetic approaches, the pseudopeptides were successfully cyclized from two L-allylglycine side chains via an alkene ring-closing metathesis reaction during the peptide synthesis. The alkene-linker was formed in a 1 : 1 E/Z isomer ratio. The resulting pseudopeptides were almost as potent as the parent peptide, increasing the activity of KLK3 over four-fold at 200 μg ml−1 (130–140 μM) concentrations.
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| 5. |
- O'Boyle, Niamh M, et al.
(author)
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Analogues of the epoxy resin monomer diglycidyl ether of Bisphenol F: effects on contact allergenic potency and cytotoxicity
- 2012
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In: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 25:11, s. 2469-2478
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Journal article (peer-reviewed)abstract
- Diglycidyl ethers of bisphenol A (DGEBA) and bisphenol F (DGEBF) are widely used as components in epoxy resin thermosetting products. They are known to cause occupational and nonoccupational allergic contact dermatitis. The aim of this study is to investigate analogues of DGEBF with regard to contact allergy and cytotoxicity. A comprehensive knowledge of the structural features that contribute to the allergenic and cytotoxic effects of DGEBF will guide the development of future novel epoxy resin systems with reduced health hazards for those coming into contact with them. It was found that the allergenic effects of DGEBF were dependent on its terminal epoxide groups. In contrast, it was found that the cytotoxicity in monolayer cell culture was dependent not only on the presence of epoxide groups but also on other structural features.
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| 6. |
- O'Boyle, Niamh M, et al.
(author)
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Epoxy Resin Monomers with Reduced Skin Sensitizing Potency
- 2014
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In: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 27:6, s. 1002-1010
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Journal article (peer-reviewed)abstract
- Epoxy resin monomers (ERMs), especially diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to commonly cause skin allergy. This research describes a number of alternative ERMs, designed with the aim of reducing the skin sensitizing potency while maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, and assessed for sensitizing potency using the in vivo murine local lymph node assay (LLNA). All six epoxy resin monomers had decreased sensitizing potencies compared to those of DGEBA and DGEBF. With respect to the LLNA EC3 value, the best of the alternative monomers had a value approximately 2.5 times higher than those of DGEBA and DGEBF. The diepoxides were reacted with triethylenetetramine, and the polymers formed were tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. Four out of the six alternative ERMs gave polymers with a thermal stability comparable to that obtained with DGEBA and DGEBF. The use of improved epoxy resin monomers with less skin sensitizing effects is a direct way to tackle the problem of contact allergy to epoxy resin systems, particularly in occupational settings, resulting in a reduction in the incidence of allergic contact dermatitis.
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