{"entity": "journal", "iuid": "948ab1a73b3e4ef48bce3aeb6abe5187", "timestamp": "2026-06-07T20:18:15.842Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/Eur%20J%20Med%20Chem.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/Eur%20J%20Med%20Chem"}}, "title": "Eur J Med Chem", "issn": "1768-3254", "issn-l": "0223-5234", "publications_count": 7, "publications": [{"entity": "publication", "iuid": "d6f97413fcc64401be69c49a50119362", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d6f97413fcc64401be69c49a50119362.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d6f97413fcc64401be69c49a50119362"}}, "title": "Structure-based virtual screening discovers potent and selective adenosine A1 receptor antagonists.", "authors": [{"family": "Matricon", "given": "Pierre", "initials": "P", "orcid": "0000-0001-9350-896X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19dcd180ddc54eb48269a1638d83ece1.json"}}, {"family": "Nguyen", "given": "Anh Tn", "initials": "AT"}, {"family": "Vo", "given": "Duc Duy", "initials": "DD"}, {"family": "Baltos", "given": "Jo-Anne", "initials": "JA"}, {"family": "Jaiteh", "given": "Mariama", "initials": "M", "orcid": "0000-0002-9229-5314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc99e1f36efa4efb8400c13d361ae17f.json"}}, {"family": "Luttens", "given": "Andreas", "initials": "A", "orcid": "0000-0003-2915-7901", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2944edc47eb4b639f1c61ae7b94b60a.json"}}, {"family": "Kampen", "given": "Stefanie", "initials": "S"}, {"family": "Christopoulos", "given": "Arthur", "initials": "A", "orcid": "0000-0003-4442-3294", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7569b7081884421e9afecc122663834e.json"}}, {"family": "Kihlberg", "given": "Jan", "initials": "J", "orcid": "0000-0002-4205-6040", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7edb4dfa7c4b4d6c8c4cf0282a9c9a1a.json"}}, {"family": "May", "given": "Lauren Therese", "initials": "LT"}, {"family": "Carlsson", "given": "Jens", "initials": "J", "orcid": "0000-0003-4623-2977", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/792c1cd4aca248dc94b967115ffa82df.json"}}], "type": "journal article", "published": "2023-09-05", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "257", "pages": "115419", "issn-l": "0223-5234"}, "abstract": "Development of subtype-selective leads is essential in drug discovery campaigns targeting G protein-coupled receptors (GPCRs). Herein, a structure-based virtual screening approach to rationally design subtype-selective ligands was applied to the A1 and A2A adenosine receptors (A1R and A2AR). Crystal structures of these closely related subtypes revealed a non-conserved subpocket in the binding sites that could be exploited to identify A1R selective ligands. A library of 4.6 million compounds was screened computationally against both receptors using molecular docking and 20 A1R selective ligands were predicted. Of these, seven antagonized the A1R with micromolar activities and several compounds displayed slight selectivity for this subtype. Twenty-seven analogs of two discovered scaffolds were designed, resulting in antagonists with nanomolar potency and up to 76-fold A1R-selectivity. Our results show the potential of structure-based virtual screening to guide discovery and optimization of subtype-selective ligands, which could facilitate the development of safer drugs.", "doi": "10.1016/j.ejmech.2023.115419", "pmid": "37301076", "labels": {"Jens Carlsson": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "S0223-5234(23)00385-9"}], "notes": [], "created": "2023-11-27T19:57:12.187Z", "modified": "2025-04-11T07:26:53.106Z"}, {"entity": "publication", "iuid": "aafba9b1723a4576ad65c4fde1e93ddc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/aafba9b1723a4576ad65c4fde1e93ddc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/aafba9b1723a4576ad65c4fde1e93ddc"}}, "title": "Development of l-Dopa-containing diketopiperazines as blood-brain barrier shuttle.", "authors": [{"family": "Cornacchia", "given": "Catia", "initials": "C"}, {"family": "Marinelli", "given": "Lisa", "initials": "L", "orcid": "0000-0001-8611-6538", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/97c00bbd21584fd7a44200f607877276.json"}}, {"family": "Di Rienzo", "given": "Annalisa", "initials": "A", "orcid": "0000-0002-9994-6968", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21b8ecd7e661415bbec3d6cc141a2ddf.json"}}, {"family": "Dimmito", "given": "Marilisa Pia", "initials": "MP"}, {"family": "Serra", "given": "Federica", "initials": "F"}, {"family": "Di Biase", "given": "Giuseppe", "initials": "G"}, {"family": "De Filippis", "given": "Barbara", "initials": "B"}, {"family": "Turkez", "given": "Hasan", "initials": "H", "orcid": "0000-0002-7046-8990", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cf2f1748757d45cabfe56fdfaccead6a.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca58bf2d214047e0ae5e38a42a0f2808.json"}}, {"family": "Bellezza", "given": "Ilaria", "initials": "I"}, {"family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}}, {"family": "Cacciatore", "given": "Ivana", "initials": "I", "orcid": "0000-0001-6253-0443", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/31661d5900cc4711923f4bf51cf47a93.json"}}], "type": "journal article", "published": "2022-12-05", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "243", "pages": "114746", "issn-l": "0223-5234"}, "abstract": "In our overall goal to develop anti-Parkinson drugs, we designed novel diketopiperazines (DKP1-6) aiming to both reach the blood-brain barrier and counteract the oxidative stress related to Parkinson's Disease (PD). The anti-Parkinson properties of DKP 1-6 were evaluated using neurotoxin-treated PC12 cells, as in vitro model of PD, while their cytotoxicity and genotoxicity potentials were investigated in newborn rat cerebral cortex (RCC) and primary human whole blood (PHWB) cell cultures. The response against free radicals was evaluated by the total antioxidant capacity (TAC) assay. Comet assay was used to detect DNA damage while the content of 8-hydroxyl-2'-deoxyguanosine (8-OH-dG) was determined as a marker of oxidative DNA damage. PAMPA-BBB and Caco-2 assays were employed to evaluate the capability of DKP1-6 to cross the membranes. Stability studies were conducted in simulated gastric and intestinal fluids and human plasma. Results showed that DKP5-6 attenuate the MPP + -induced cell death on a nanomolar scale, but a remarkable effect was observed for DKP6 on Nrf2 activation that leads to the expression of genes involved in oxidative stress response thus increasing glutathione biosynthesis and ROS buffering. DKP5-6 resulted in no toxicity for RCC neurons and PHWB cells exposed to 10-500 nM concentrations during 24 h as determined by MTT and LDH assays and TAC levels were not altered in both cultured cell types. No significant difference in the induction of DNA damage was observed for DKP5-6. Both DKPs resulted stable in simulated gastric fluids (t1/2 > 22h). In simulated intestinal fluids, DKP5 underwent immediate hydrolysis while DKP6 showed a half-life higher than 3 h. In human plasma, DKP6 resulted quite stable. DKP6 displayed both high BBB and Caco-2 permeability confirming that the DKP scaffold represents a useful tool to improve the crossing of drugs through the biological membranes.", "doi": "10.1016/j.ejmech.2022.114746", "pmid": "36099749", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "S0223-5234(22)00648-1"}], "notes": [], "created": "2023-12-04T14:58:09.279Z", "modified": "2025-04-29T07:06:35.664Z"}, {"entity": "publication", "iuid": "fba9274fabaa4a3f8362c8b788fd889d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fba9274fabaa4a3f8362c8b788fd889d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fba9274fabaa4a3f8362c8b788fd889d"}}, "title": "Anthraquinone derivatives as ADP-competitive inhibitors of liver pyruvate kinase.", "authors": [{"family": "Nain-Perez", "given": "Amalyn", "initials": "A"}, {"family": "Foller F\u00fcchtbauer", "given": "Anders", "initials": "A"}, {"family": "H\u00e5versen", "given": "Liliana", "initials": "L"}, {"family": "Lulla", "given": "Aleksei", "initials": "A"}, {"family": "Gao", "given": "Chunxia", "initials": "C"}, {"family": "Matic", "given": "Josipa", "initials": "J"}, {"family": "Monjas", "given": "Leticia", "initials": "L"}, {"family": "Rodr\u00edguez", "given": "Alexandra", "initials": "A"}, {"family": "Brear", "given": "Paul", "initials": "P"}, {"family": "Kim", "given": "Woonghee", "initials": "W"}, {"family": "Hyv\u00f6nen", "given": "Marko", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}, {"family": "Uhlen", "given": "Mathias", "initials": "M"}, {"family": "Gr\u00f8tli", "given": "Morten", "initials": "M"}], "type": "journal article", "published": "2022-04-15", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "234", "pages": "114270", "issn-l": "0223-5234"}, "abstract": "Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP production during liver cell glycolysis and is considered a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). In this study, we report the first ADP-competitive PKL inhibitors and identify several starting points for the further optimization of these inhibitors. Modeling and structural biology guided the optimization of a PKL-specific anthraquinone-based compound. A structure-activity relationship study of 47 novel synthetic derivatives revealed PKL inhibitors with half-maximal inhibitory concentration (IC50) values in the 200 nM range. Despite the difficulty involved in studying a binding site as exposed as the ADP site, these derivatives feature expanded structural diversity and chemical spaces that may be used to improve their inhibitory activities against PKL. The obtained results expand the knowledge of the structural requirements for interactions with the ADP-binding site of PKL.", "doi": "10.1016/j.ejmech.2022.114270", "pmid": "35290845", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "S0223-5234(22)00172-6"}], "notes": [], "created": "2023-12-04T15:02:17.932Z", "modified": "2023-12-04T15:02:17.936Z"}, {"entity": "publication", "iuid": "e1572a37f421499486b9ac1d5ef5157d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e1572a37f421499486b9ac1d5ef5157d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e1572a37f421499486b9ac1d5ef5157d"}}, "title": "Novel anti-Alzheimer phenol-lipoyl hybrids: Synthesis, physico-chemical characterization, and biological evaluation.", "authors": [{"family": "Pagoni", "given": "Aikaterini", "initials": "A"}, {"family": "Marinelli", "given": "Lisa", "initials": "L"}, {"family": "Di Stefano", "given": "Antonio", "initials": "A"}, {"family": "Ciulla", "given": "Michele", "initials": "M"}, {"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}, {"family": "Vassiliou", "given": "Stamatia", "initials": "S"}, {"family": "Cacciatore", "given": "Ivana", "initials": "I", "orcid": "0000-0001-6253-0443", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/31661d5900cc4711923f4bf51cf47a93.json"}}], "type": "journal article", "published": "2020-01-15", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "issn-l": "0223-5234", "volume": "186", "issue": null, "pages": "111880"}, "abstract": "To date, drugs that hit a single target are inadequate for the treatment of neurodegenerative diseases, such as Alzheimer's or Parkinson's diseases. The development of multitarget ligands, able to interact with the different pathways involved in the progession of these disorders, represents a great challenge for medicinal chemists. In this context, we report here the synthesis and biological evaluation of phenol-lipoyl hybrids (SV1-13), obtained via a linking strategy, to take advantage of the synergistic effect due to the antioxidant portions and anti-amyloid properties of the single constituents present in the hybrid molecule. Biological results showed that SV5 and SV10 possessed the best protective activity against A\u03b21-42 induced neurotoxicity in differentiated SH-SY5Y cells. SV9 and SV10 showed remarkable antioxidant properties due to their ability to counteract the damage caused by H2O2 in SHSY-5Y-treated cells. Hovewer, SV5, showing moderate antioxidant and good neuroprotective activities, resulted the best candidate for further experiments since it also resulted stable both simulated and plasma fluids.", "doi": "10.1016/j.ejmech.2019.111880", "pmid": "31753513", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "S0223-5234(19)31032-3"}], "notes": [], "created": "2020-09-25T13:13:46.240Z", "modified": "2022-11-04T11:32:15.508Z"}, {"entity": "publication", "iuid": "97c65e7752694d63bd3b452d7defbf7a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/97c65e7752694d63bd3b452d7defbf7a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/97c65e7752694d63bd3b452d7defbf7a"}}, "title": "Synthetic approaches to radiochemical probes for imaging of bacterial infections.", "authors": [{"family": "Dutta", "given": "Jyotibon", "initials": "J"}, {"family": "Naicker", "given": "Tricia", "initials": "T"}, {"family": "Ebenhan", "given": "Thomas", "initials": "T"}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI"}, {"family": "Govender", "given": "Thavendran", "initials": "T"}], "type": "journal article", "published": "2017-06-16", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "133", "issue": null, "pages": "287-308", "issn-l": "0223-5234"}, "abstract": "This present review provides an account on the available synthetic strategies employed to radiolabel commercial and potential bacteria-selective probes for tomographic imaging. These molecular probes encompass leukocytes, antibodies, small molecules, peptides, antibiotics, macrolides, vitamins, oligomers and siderophores. Although this technique has shown to be a valuable tool for non-invasive infection imaging, more development is required to create easy-to-radiolabel kit solutions/procedures for the preparation of the probes.", "doi": "10.1016/j.ejmech.2017.03.060", "pmid": "28395216", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0223-5234(17)30227-1"}], "notes": [], "created": "2018-12-05T11:39:27.289Z", "modified": "2018-12-05T11:39:27.308Z"}, {"entity": "publication", "iuid": "40892b9dae13483bb4b20d9d0dc4f3e5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/40892b9dae13483bb4b20d9d0dc4f3e5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/40892b9dae13483bb4b20d9d0dc4f3e5"}}, "title": "Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer's disease.", "authors": [{"family": "Maqbool", "given": "Mudasir", "initials": "M"}, {"family": "Mobashir", "given": "Mohammad", "initials": "M"}, {"family": "Hoda", "given": "Nasimul", "initials": "N"}], "type": "journal article", "published": "2016-01-01", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "107", "issue": null, "pages": "63-81", "issn-l": "0223-5234"}, "abstract": "Neurodegenerative diseases are among the most challenging diseases with poorly known mechanism of cause and paucity of complete cure. Out of all the neurodegenerative diseases, Alzheimer's disease is the most devastating and loosening of thinking and judging ability disease that occurs in the old age people. Many hypotheses came forth in order to explain its causes. In this review, we have enlightened Glycogen Synthase Kinase-3 which has been considered as a concrete cause for Alzheimer's disease. Plaques and Tangles (abnormal structures) are the basic suspects in damaging and killing of nerve cells wherein Glycogen Synthase Kinase-3 has a key role in the formation of these fatal accumulations. Various Glycogen Synthase Kinase-3 inhibitors have been reported to reduce the amount of amyloid-beta as well as the tau hyperphosphorylation in both neuronal and nonneuronal cells. Additionally, Glycogen Synthase Kinase-3 inhibitors have been reported to enhance the adult hippocampal neurogenesis in vivo as well as in vitro. Keeping the chemotype of the reported Glycogen Synthase Kinase-3 inhibitors in consideration, they may be grouped into natural inhibitors, inorganic metal ions, organo-synthetic, and peptide like inhibitors. On the basis of their mode of binding to the constituent enzyme, they may also be grouped as ATP, nonATP, and allosteric binding sites competitive inhibitors. ATP competitive inhibitors were known earlier inhibitors but they lack efficient selectivity. This led to find the new ways for the enzyme inhibition.", "doi": "10.1016/j.ejmech.2015.10.018", "pmid": "26562543", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0223-5234(15)30300-7"}], "notes": [], "created": "2018-12-05T08:51:35.904Z", "modified": "2018-12-05T08:51:35.937Z"}, {"entity": "publication", "iuid": "b6cd91820b3843c19c3de40d41e4c0be", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b6cd91820b3843c19c3de40d41e4c0be.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b6cd91820b3843c19c3de40d41e4c0be"}}, "title": "Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo.", "authors": [{"family": "Caraballo", "given": "R\u00e9mi", "initials": "R"}, {"family": "Larsson", "given": "Mikael", "initials": "M"}, {"family": "Nilsson", "given": "Stefan K", "initials": "SK"}, {"family": "Ericsson", "given": "Madelene", "initials": "M"}, {"family": "Qian", "given": "Weixing", "initials": "W"}, {"family": "Nguyen Tran", "given": "Nam Phuong", "initials": "NP"}, {"family": "Kindahl", "given": "Tomas", "initials": "T"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Saar", "given": "Valeria", "initials": "V"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Olivecrona", "given": "Gunilla", "initials": "G"}, {"family": "Enquist", "given": "Per-Anders", "initials": "PA"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}], "type": "journal article", "published": "2015-10-20", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "103", "issue": null, "pages": "191-209", "issn-l": "0223-5234"}, "abstract": "The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun.2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo.", "doi": "10.1016/j.ejmech.2015.08.058", "pmid": "26355531", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0223-5234(15)30241-5"}], "notes": [], "created": "2018-12-05T12:03:58.314Z", "modified": "2018-12-05T12:03:58.333Z"}], "created": "2018-12-05T08:51:35.918Z", "modified": "2020-11-27T13:12:57.055Z"}