| 1. |
- Carlborg, Carl Fredrik, et al.
(författare)
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Biosticker : patterned microfluidic stickers for rapid integration with microarrays
- 2011
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Ingår i: The 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS 2011). - : Chemical and Biological Microsystems Society. - 9781618395955 ; , s. 311-313
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Konferensbidrag (refereegranskat)abstract
- We present a one-step, reversible, and biocompatible bonding method of a stiff patterned microfluidic "Biosticker", based on off-stoichiometry thiol-ene (OSTE) polymers [1], to state-of-the-art spotted microarray surfaces. The method aims at improving and simplifying the batch back-end processing of microarrays. We illustrate its ease of use in two applications: a high sensitivity flow-through protein assay; and a DNA-hybridization test. Read-out was performed in a standard highvolume array scanner, and showed excellent spot homogeneity and intensity. The Biosticker is aimed to be a plug-in for existing microarray platforms to enable faster protein assays and DNA hybridizations through mass transport optimization.
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| 2. |
- Lolli, M. L., et al.
(författare)
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Bioisosteres of Indomethacin as Inhibitors of Aldo-Keto Reductase 1C3
- 2019
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Ingår i: Acs Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 10:4, s. 437-443
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Tidskriftsartikel (refereegranskat)abstract
- Aldo-keto reductase 1C3 (AKR1C3) is an attractive target in drug design for its role in resistance to anticancer therapy. Several nonsteroidal anti-inflammatory drugs such as indomethacin are known to inhibit AKR1C3 in a nonselective manner because of COX-off target effects. Here we designed two indomethacin analogues by proposing a bioisosteric connection between the indomethacin carboxylic acid function and either hydroxyfurazan or hydroxy triazole rings. Both compounds were found to target AKR1C3 in a selective manner. In particular, hydroxyfurazan derivative is highly selective for AKR1C3 over the 1C2 isoform (up to 90-times more) and inactive on COX enzymes. High-resolution crystal structure of its complex with AKR1C3 shed light onto the binding mode of the new inhibitors. In cell-based assays (on colorectal and prostate cancer cells), the two indomethacin analogues showed higher potency than indomethacin. Therefore, these two AKR1C3 inhibitors can be used to provide further insight into the role of AKR1C3 in cancer. © 2019 American Chemical Society.
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| 3. |
- Pippione, Agnese C., et al.
(författare)
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Hydroxyazole scaffold-based Plasmodium falciparum dihydroorotate dehydrogenase inhibitors : Synthesis, biological evaluation and X-ray structural studies
- 2019
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 163, s. 266-280
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Tidskriftsartikel (refereegranskat)abstract
- Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) has been clinically validated as a target for antimalarial drug discovery, as a triazolopyrimidine class inhibitor (DSM265) is currently undergoing clinical development. Here, we have identified new hydroxyazole scaffold-based PfDHODH inhibitors belonging to two different chemical series. The first series was designed by a scaffold hopping strategy that exploits the use of hydroxylated azoles. Within this series, the hydroxythiadiazole 3 was identified as the best selective PfDHODH inhibitor (IC50 12.0 μM). The second series was designed by modulating four different positions of the hydroxypyrazole scaffold. In particular, hydroxypyrazoles 7e and 7f were shown to be active in the low μM range (IC50 2.8 and 5.3 μM, respectively). All three compounds, 3, 7e and 7f showed clear selectivity over human DHODH (IC50 > 200 μM), low cytotoxicity, and retained micromolar activity in P. falciparum-infected erythrocytes. The crystallographic structures of PfDHODH in complex with compounds 3 and 7e proved their binding mode, supplying essential data for future optimization of these scaffolds.
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