{"entity": "researcher", "timestamp": "2026-06-17T07:39:15.916Z", "family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "affiliations": [], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0"}}, "publications": [{"entity": "publication", "iuid": "4b5d46046c5b4b679bda60abe8aaf0d4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4b5d46046c5b4b679bda60abe8aaf0d4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4b5d46046c5b4b679bda60abe8aaf0d4"}}, "title": "Novel styryl-thiazole hybrids as potential anti-Alzheimer's agents.", "authors": [{"family": "Gouleni", "given": "Niki", "initials": "N"}, {"family": "Di Rienzo", "given": "Annalisa", "initials": "A", "orcid": "0000-0002-9994-6968", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21b8ecd7e661415bbec3d6cc141a2ddf.json"}}, {"family": "Y\u0131lmaz", "given": "Ahmet", "initials": "A"}, {"family": "Selvitopi", "given": "Harun", "initials": "H", "orcid": "0000-0001-5958-7625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a48920bce92d48ba8da645c87d2738ce.json"}}, {"family": "Arslan", "given": "Mehmet Enes", "initials": "ME", "orcid": "0000-0002-1600-2305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c5dd8a766b948efa5f040ceb43e60a6.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca58bf2d214047e0ae5e38a42a0f2808.json"}}, {"family": "Turkez", "given": "Hasan", "initials": "H", "orcid": "0000-0002-7046-8990", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cf2f1748757d45cabfe56fdfaccead6a.json"}}, {"family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}}, {"family": "Vassiliou", "given": "Stamatia", "initials": "S", "orcid": "0000-0002-0734-6579", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1aa27118ccdf4c37af17b810e51140fe.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": "2023-11-15", "journal": {"title": "RSC Med Chem", "issn": "2632-8682", "volume": "14", "issue": "11", "pages": "2315-2326", "issn-l": null}, "abstract": "In this study, combining the thiazole and cinnamoyl groups into the styryl-thiazole scaffold, a series of novel styryl-thiazole hybrids (6a-p) was rationally designed, synthesized, and evaluated by the multi-target-directed ligands strategy as potential candidates for the treatment of Alzheimer's disease (AD). Hybrids 6e and 6i are the most promising among the synthesized hybrids since they are able to significantly increase cell viabilities in A\u03b21-42-exposed-human neuroblastoma cell line (6i at the concentration of 50 \u03bcg mL-1 and 6e at the concentration of 25 \u03bcg mL-1 resulted in \u223c34% and \u223c30% increase in cell viabilities, respectively). Compounds 6e and 6i exhibit highly AChE inhibitory properties in the experimental AD model at 375.6 \u00b1 18.425 mU mL-1 and 397.6 \u00b1 32.152 mU mL-1, respectively. Moreover, these data were also confirmed by docking studies and in vitro enzyme inhibition assays. Compared to hybrid 6e and according to the results, 6i also has the highest potential against A\u03b21-42 aggregation with over 80% preventive activity. The in silico prediction of the physicochemical properties confirms that 6i possesses a better profile compared to 6e. Therefore, compound 6i presents a promising multi-targeted active molecular profile for treating AD considering the multifactorial nature of AD, and it is reasonable to deepen its mechanisms of action in an in vivo experimental model of AD.", "doi": "10.1039/d3md00308f", "pmid": "38020070", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC10650344"}, {"db": "pii", "key": "d3md00308f"}], "notes": [], "created": "2023-12-04T14:46:29.246Z", "modified": "2025-04-11T07:24:01.942Z"}, {"entity": "publication", "iuid": "1d54535a9ac04512b5312e6ad061ad69", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1d54535a9ac04512b5312e6ad061ad69.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1d54535a9ac04512b5312e6ad061ad69"}}, "title": "Anticancer Potential of Novel Cinnamoyl Derivatives against U87MG and SHSY-5Y Cell Lines.", "authors": [{"family": "Gouleni", "given": "Niki", "initials": "N"}, {"family": "Di Rienzo", "given": "Annalisa", "initials": "A", "orcid": "0000-0002-9994-6968", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21b8ecd7e661415bbec3d6cc141a2ddf.json"}}, {"family": "Oner", "given": "Sena", "initials": "S"}, {"family": "Karag\u00f6z", "given": "Ceren", "initials": "C"}, {"family": "Arslan", "given": "Mehmet Enes", "initials": "ME"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}, {"family": "Turkez", "given": "Hasan", "initials": "H", "orcid": "0000-0002-7046-8990", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cf2f1748757d45cabfe56fdfaccead6a.json"}}, {"family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}}, {"family": "Vassiliou", "given": "Stamatia", "initials": "S", "orcid": "0000-0002-0734-6579", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1aa27118ccdf4c37af17b810e51140fe.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": "2023-11-10", "journal": {"title": "Anticancer Agents Med Chem", "issn": "1875-5992", "issn-l": null}, "abstract": "Glioblastoma multiforme (GBM) is probably the most malignant and aggressive brain tumor belonging to the class of astrocytomas. The considerable aggressiveness and high malignancy of GBM make it a tumor that is difficult to treat. Here, we report the synthesis and biological evaluation of eighteen novel cinnamoyl derivatives (3a-i and 4a-i) to obtain more effective antitumor agents against GBM.\n\nThe chemical structures of novel cinnamoyl derivatives (3a-i and 4a-i) were confirmed by NMR and MS analyses. The physicochemical properties and evaluation of the ADME profile of 3a-i and 4a-i were performed by the preADMETlab2.0 web program. Cinnamoyl derivatives 3a-i and 4a-i were tested in vitro for their cytotoxicity against the human healthy fibroblast (HDFa) cells using an MTT cell viability assay. Derivatives with no toxicity on HDFa cells were tested both on human glioblastoma (U87MG) and neuroblastoma (SHSY- 5Y) cells, chosen as an experimental model of brain tumors. Cell death mechanisms were analyzed by performing flow cytometry analyses.\n\nCinnamoyl derivatives 3a-i and 4a-i showed good physicochemical and ADME properties suggesting that these compounds could be developed as oral drugs endowed with a high capability to cross the blood-brain barrier. Compounds (E)-1-methoxy-4-(2-(phenylsulfonyl)vinyl)benzene (2c) and (E)-N-benzyl-N-(2- (cyclohexylamino)-2-oxoethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (3e) did not show cytotoxicity on healthy human fibroblast cells up to 100 \u03bcg/mL. The most anticarcinogenic molecule, compound 3e, emerged as the most potent anticancer candidate in this study. Flow cytometry results showed that compound 3e (25 \u03bcg/mL) application resulted in nearly 86% and 84% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively. Compound 2c (25 \u03bcg/mL) resulted in 81% and 82% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively.\n\nCinnamoyl derivative 3e inhibits the proliferation of cultured U87MG and SHSY-5Y cells by inducing apoptosis. Further detailed research will be conducted to confirm these data in in vivo experimental animal models.", "doi": "10.2174/0118715206266917231106064937", "pmid": "37957910", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "ACAMC-EPUB-136069"}], "notes": [], "created": "2023-12-04T14:48:04.130Z", "modified": "2023-12-04T14:48:15.701Z"}, {"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": "9da9a80f2d2f4eb081de73a7584fe558", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9da9a80f2d2f4eb081de73a7584fe558.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9da9a80f2d2f4eb081de73a7584fe558"}}, "title": "Toxicity of Glycyl-l-Prolyl-l-Glutamate Pseudotripeptides: Cytotoxic, Oxidative, Genotoxic, and Embryotoxic Perspectives.", "authors": [{"family": "Turkez", "given": "Hasan", "initials": "H", "orcid": "0000-0002-7046-8990", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cf2f1748757d45cabfe56fdfaccead6a.json"}}, {"family": "Ozdemir Tozlu", "given": "Ozlem", "initials": "O", "orcid": "0000-0002-5472-8174", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f64b15273ce49348b9ffebf5230ea11.json"}}, {"family": "Tatar", "given": "Arzu", "initials": "A", "orcid": "0000-0002-4486-2695", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3b34bfb83ab14a95bc03c974d39f816c.json"}}, {"family": "Arslan", "given": "Mehmet Enes", "initials": "ME", "orcid": "0000-0002-1600-2305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c5dd8a766b948efa5f040ceb43e60a6.json"}}, {"family": "Cadirci", "given": "Kenan", "initials": "K", "orcid": "0000-0002-2765-4288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/305106d191054c26a2de64f9ca54437f.json"}}, {"family": "Marinelli", "given": "Lisa", "initials": "L", "orcid": "0000-0001-8611-6538", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/97c00bbd21584fd7a44200f607877276.json"}}, {"family": "Yapca", "given": "Omer Erkan", "initials": "OE", "orcid": "0000-0002-5578-0126", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ea9b4f98ad24d549984a2c9e00a58d9.json"}}, {"family": "Cacciatore", "given": "Ivana", "initials": "I", "orcid": "0000-0001-6253-0443", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/31661d5900cc4711923f4bf51cf47a93.json"}}, {"family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca58bf2d214047e0ae5e38a42a0f2808.json"}}], "type": "journal article", "published": "2022-11-19", "journal": {"title": "J Toxicol", "issn": "1687-8191", "volume": "2022", "pages": "3775194", "issn-l": null}, "abstract": "The tripeptide H-Gly-Pro-Glu-OH (GPE) and its analogs began to take much interest from scientists for developing effective novel molecules in the treatment of several disorders including Alzheimer's disease, Parkinson's disease, and stroke. The peptidomimetics of GPEs exerted significant biological properties involving anti-inflammatory, antiapoptotic, and anticancer properties. The assessments of their hematological toxicity potentials are critically required for their possible usage in further preclinical and clinical trials against a wide range of pathological conditions. However, there is so limited information on the safety profiling of GPE and its analogs on human blood tissue from cytotoxic, oxidative, and genotoxic perspectives. And, their embryotoxicity potentials were not investigated yet. Therefore, in this study, measurements of mitochondrial viability (using MTT assay) and lactate dehydrogenase (LDH) release as well as total antioxidant capacity (TAC) assays were performed on cultured human whole blood cells after treatment with GPE and its three novel peptidomimetics for 72 h. Sister chromatid exchange (SCE), micronucleus (MN), and 8-oxo-2-deoxyguanosine (8-OH-dG) assays were performed for determining the genotoxic damage potentials. In addition, the nuclear division index (NDI) was figured out for revealing their cytostatic potentials. Embryotoxicity assessments were performed on cultured human pluripotent NT2 embryonal carcinoma cells by MTT and LDH assays. The present results from cytotoxicity, oxidative, genotoxicity, and embryotoxicity testing clearly propounded that GPEs had good biosafety profiles and were trouble-free from the toxicological point of view. Noncytotoxic, antioxidative, nongenotoxic, noncytostatic, and nonembryotoxic features of GPE analogs are worthwhile exploring further and may exert high potentials for improving the development of novel disease-modifying agents.", "doi": "10.1155/2022/3775194", "pmid": "36444193", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC9701129"}], "notes": [], "created": "2023-12-04T14:53:09.961Z", "modified": "2023-12-04T14:53:10.249Z"}, {"entity": "publication", "iuid": "bdb94abf6bb749cba40f945d5699263b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bdb94abf6bb749cba40f945d5699263b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bdb94abf6bb749cba40f945d5699263b"}}, "title": "Ameliorative Effects by Hexagonal Boron Nitride Nanoparticles against Beta Amyloid Induced Neurotoxicity.", "authors": [{"family": "Aydin", "given": "Nursah", "initials": "N"}, {"family": "Turkez", "given": "Hasan", "initials": "H", "orcid": "0000-0002-7046-8990", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cf2f1748757d45cabfe56fdfaccead6a.json"}}, {"family": "Tozlu", "given": "Ozlem Ozdemir", "initials": "OO"}, {"family": "Arslan", "given": "Mehmet Enes", "initials": "ME", "orcid": "0000-0002-1600-2305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c5dd8a766b948efa5f040ceb43e60a6.json"}}, {"family": "Yavuz", "given": "Mehmet", "initials": "M"}, {"family": "Sonmez", "given": "Erdal", "initials": "E"}, {"family": "Ozpolat", "given": "Ozgur F\u0131rat", "initials": "OF", "orcid": "0000-0002-4533-4368", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0584d9e39ecf4136bbb259da53314ca8.json"}}, {"family": "Cacciatore", "given": "Ivana", "initials": "I", "orcid": "0000-0001-6253-0443", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/31661d5900cc4711923f4bf51cf47a93.json"}}, {"family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca58bf2d214047e0ae5e38a42a0f2808.json"}}], "type": "journal article", "published": "2022-08-05", "journal": {"title": "Nanomaterials (Basel)", "issn": "2079-4991", "volume": "12", "issue": "15", "issn-l": null}, "abstract": "Alzheimer\u2019s disease (AD) is considered as the most common neurodegenerative disease. Extracellular amyloid beta (A\u03b2) deposition is a hallmark of AD. The options based on degradation and clearance of A\u03b2 are preferred as promising therapeutic strategies for AD. Interestingly, recent findings indicate that boron nanoparticles not only act as a carrier but also play key roles in mediating biological effects. In the present study, the aim was to investigate the effects of different concentrations (0\u2212500 mg/L) of hexagonal boron nitride nanoparticles (hBN-NPs) against neurotoxicity by beta amyloid (A\u03b21-42) in differentiated human SH-SY5Y neuroblastoma cell cultures for the first time. The synthesized hBN-NPs were characterized by X-ray diffraction (XRD) measurements, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A\u03b21-42-induced neurotoxicity and therapeutic potential by hBN-NPs were assessed on differentiated SH-SY5Y cells using MTT and LDH release assays. Levels of total antioxidant capacity (TAC) and total oxidant status (TOS), expression levels of genes associated with AD and cellular morphologies were examined. The exposure to A\u03b21-42 significantly decreased the rates of viable cells which was accompanied by elevated TOS level. A\u03b21-42 induced both apoptotic and necrotic cell death. A\u03b2 exposure led to significant increases in expression levels of APOE, BACE 1, EGFR, NCTSN and TNF-\u03b1 genes and significant decreases in expression levels of ADAM 10, APH1A, BDNF, PSEN1 and PSENEN genes (p < 0.05). All the A\u03b21-42-induced neurotoxic insults were inhibited by the applications with hBN-NPs. hBN-NPs also suppressed the remarkable elevation in the signal for A\u03b2 following exposure to A\u03b21-42 for 48 h. Our results indicated that hBN-NPs could significantly prevent the neurotoxic damages by A\u03b2. Thus, hBN-NPs could be a novel and promising anti-AD agent for effective drug development, bio-nano imaging or drug delivery strategies.", "doi": "10.3390/nano12152690", "pmid": "35957121", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC9370266"}, {"db": "pii", "key": "nano12152690"}], "notes": [], "created": "2023-12-04T14:58:15.087Z", "modified": "2023-12-04T14:58:15.213Z"}, {"entity": "publication", "iuid": "602f6de7dd804796b73a794658ed41e8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/602f6de7dd804796b73a794658ed41e8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/602f6de7dd804796b73a794658ed41e8"}}, "title": "Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates.", "authors": [{"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Cacciatore", "given": "Ivana", "initials": "I"}, {"family": "Arslan", "given": "Mehmet Enes", "initials": "ME"}, {"family": "Fornasari", "given": "Erika", "initials": "E"}, {"family": "Marinelli", "given": "Lisa", "initials": "L"}, {"family": "Di Stefano", "given": "Antonio", "initials": "A", "orcid": "0000-0002-3042-2234", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/413d1857e18c4eef8929bb9ceedc5af0.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "journal article", "published": "2020-05-09", "journal": {"title": "Biomolecules", "issn": "2218-273X", "issn-l": null, "volume": "10", "issue": "5", "pages": "737"}, "abstract": "Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer's disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of all-trans retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 (A\u03b2) peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), \u03b1- and \u03b2-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against 1-42A\u03b2-induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by 1-42A\u03b2 exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.1-42", "doi": "10.3390/biom10050737", "pmid": "32397415", "labels": {"Adil Mardinoglu": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "biom10050737"}, {"db": "pmc", "key": "PMC7277666"}], "notes": [], "created": "2020-11-30T03:11:36.175Z", "modified": "2022-11-04T11:32:15.009Z"}]}