{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:52:54Z","timestamp":1787500374559,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2017\/27\/B\/NZ7\/01767"],"award-info":[{"award-number":["2017\/27\/B\/NZ7\/01767"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["PBsd20"],"award-info":[{"award-number":["PBsd20"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neurodegenerative and mental diseases are serious medical, economic and social problems. Neurodegeneration is referred to as a pathological condition associated with damage to nerve cells leading to their death. Treatment of neurodegenerative diseases is at present symptomatic only, and novel drugs are urgently needed which would be able to stop disease progression. We performed screening of reactive oxygen species, reactive nitrogen species, glutathione and level intracellular Ca2+. The studies were assessed using one-way ANOVA of variance with Dunnett\u2019s post hoc test. Previously, we reported D2AAK1 as a promising compound for the treatment of neurodegenerative and mental disorders. Here, we show a screening of D2AAK1 derivatives aimed at the selection of the compound with the most favorable pharmacological profile. Selected compounds cause an increase in the proliferation of a hippocampal neuron-like cell line, changes in the levels of reactive oxygen and nitrogen forms, reduced glutathione and a reduced intracellular calcium pool. Upon analyzing the structure\u2013activity relationship, we selected the compound with the most favorable profile for a neuroprotective activity for potential application in the treatment of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/molecules27072239","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:28:39Z","timestamp":1648675719000},"page":"2239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Screening and Structure\u2013Activity Relationship of D2AAK1 Derivatives for Potential Application in the Treatment of Neurodegenerative Diseases"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2160-9424","authenticated-orcid":false,"given":"Oliwia","family":"Kosz\u0142a","sequence":"first","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Faculty of Pharmacy, Medical University of Lublin, 4 A Chodzki St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-0042","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"So\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, 1 Pigonia St., 35-310 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-8248","authenticated-orcid":false,"given":"Piotr","family":"St\u0119pnicki","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Faculty of Pharmacy, Medical University of Lublin, 4 A Chodzki St., 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-9623","authenticated-orcid":false,"given":"Agnieszka A.","family":"Kaczor","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Faculty of Pharmacy, Medical University of Lublin, 4 A Chodzki St., 20-093 Lublin, Poland"},{"name":"School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1242\/dmm.030205","article-title":"Neurodegenerative Disease: Models, Mechanisms, and a New Hope","volume":"10","author":"Gitler","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hussain, R., Zubair, H., Pursell, S., and Shahab, M. (2018). Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches. Brain Sci., 8.","DOI":"10.3390\/brainsci8090177"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1080\/17460441.2019.1623784","article-title":"Cell Death Assays for Neurodegenerative Disease Drug Discovery","volume":"14","author":"Linsley","year":"2019","journal-title":"Expert Opin. 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