{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:31:19Z","timestamp":1785429079734,"version":"3.56.0"},"reference-count":104,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"crossref","award":["APVV-22-0133"],"award-info":[{"award-number":["APVV-22-0133"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"crossref","award":["APVV-23-0349"],"award-info":[{"award-number":["APVV-23-0349"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"crossref"}]},{"award":["APVV-22-0133"],"award-info":[{"award-number":["APVV-22-0133"]}],"id":[{"id":"https:\/\/ror.org\/037nx0e70","id-type":"ROR","asserted-by":"publisher"}]},{"award":["APVV-23-0349"],"award-info":[{"award-number":["APVV-23-0349"]}],"id":[{"id":"https:\/\/ror.org\/037nx0e70","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Scientific Grant Agency of the Ministry of Education, Research, Development and Youth of the Slovak Republic","award":["VEGA 1\/0429\/21"],"award-info":[{"award-number":["VEGA 1\/0429\/21"]}]},{"name":"Faculty of Pharmacy, Comenius University Bratislava","award":["FaF\/18\/2025"],"award-info":[{"award-number":["FaF\/18\/2025"]}]},{"award":["FaF\/18\/2025"],"award-info":[{"award-number":["FaF\/18\/2025"]}],"id":[{"id":"https:\/\/ror.org\/0587ef340","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Comenius University Bratislava","award":["UK\/3033\/2024"],"award-info":[{"award-number":["UK\/3033\/2024"]}]},{"award":["UK\/3033\/2024"],"award-info":[{"award-number":["UK\/3033\/2024"]}],"id":[{"id":"https:\/\/ror.org\/0587ef340","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This research paper focused on the synthesis of 1-[2-hydroxy-3-(phenylcarbamoyloxy)propyl]-4-(R1, R2-substituted phenyl)piperazin-1-ium chlorides (I)\u2013(III), containing R1, R2 = H, Cl and\/or OCH3, and the evaluation of some of their physicochemical parameters. The in vitro biological investigation of these N-arylpiperazine (NAP) derivatives consisted in assessing their impact on purinergic P2X7-associated signaling, that is, the evaluation of antioxidant, anti-inflammatory and immunomodulatory characteristics. The ultraviolet type C (UVC) irradiation (\u03bb = 254 nm, 0.954 kJ\/m2) induced a pronounced stress response in human leukocytes without marked cytotoxicity while maintaining high cell viability (\u226590%), as evidenced by increased interleukin (IL)-1\u03b2 production (94%), elevated IL-1\u03b2 mRNA expression, enhanced lipid peroxidation (66%), and increased intracellular adenosine 5\u2032-triphosphate (ATP; 97%), respectively. Under basal conditions, these lipophilic NAPs, defined with logarithmic values of retention (capacity) factors corresponding to 100% water in isocratic elution RP-HPLC, i.e., kw descriptors (varying from 2.3829 to 4.3689), and isocratic chromatographic hydrophobicity index (\u03c60) parameters (ranging from 0.7578 to 0.8842), reduced IL-1\u03b2 production (by 26\u201363%) and enhanced superoxide dismutase (SOD) activity (up to 64%) without inducing oxidative damage. Under UVC-induced stress, all evaluated compounds decreased lipid peroxidation (up to 45%) and significantly increased antioxidant enzyme activities, including SOD (up to 223%) as well as catalase (up to 145%). The observed effects were associated with changes in intracellular ATP levels and redox-related parameters. In the experiments described in this paper, intracellular ATP was measured so that no direct conclusions could be drawn regarding the extracellular ATP-dependent activation of purinergic receptors, including P2X7. Overall, the results demonstrated that variations within the structure of these NAPs significantly affected compounds\u2019 biological activity, highlighting their potential for further optimization as cytoprotective and anti-inflammatory agents.<\/jats:p>","DOI":"10.3390\/life16071046","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:11:49Z","timestamp":1782234709000},"page":"1046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New N-Arylpiperazine-Based Compounds as Potential Inhibitors of Purinergic P2X7-Associated Signaling"],"prefix":"10.3390","volume":"16","author":[{"given":"Gabriela","family":"Greifov\u00e1","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University Bratislava, Odboj\u00e1rov 10, SK-820 18 Bratislava 218, P.O. BOX 90 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9536-4074","authenticated-orcid":false,"given":"Martina","family":"Hr\u010dka Dubni\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University Bratislava, Odboj\u00e1rov 10, SK-820 18 Bratislava 218, P.O. BOX 90 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2421-9259","authenticated-orcid":false,"given":"Dominika","family":"N\u00e1dask\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University Bratislava, Odboj\u00e1rov 10, SK-820 18 Bratislava 218, P.O. 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