{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:09:34Z","timestamp":1779188974068,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A protocol through propargyl moiety on pyrrole ring cyclization with ammonium acetate was demonstrated. With this protocol, 11 pyrrolo[1,2\u2010\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrazine derivatives were synthesized, and their antiproliferative activity against the U87MG glioblastoma cell line was evaluated. Among the synthesized compounds, a naphthyl\u2010substituted derivative (\n                    <jats:bold>3g<\/jats:bold>\n                    ) exhibited the most potent in vitro activity with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 60\u2009\u00b5M, and showed no antiproliferative effect against human dermal fibroblast (HDF) cells up to 100\u2009\u03bcM. Gene expression analysis of U87MG cells treated with\n                    <jats:bold>3g<\/jats:bold>\n                    revealed a significant upregulation of key genes involved in apoptosis (CASP8, CASP9, CASP3, BAX, BCL2), autophagy (ATG3, ATG5), necroptosis (RIPK1), and DNA damage repair (PARP1) suggesting a multifaceted cell death mechanism. Furthermore, the in vivo safety profile of compound\n                    <jats:bold>3g<\/jats:bold>\n                    was assessed in an animal model by evaluating renal (BUN, creatinine) and hepatic (AST, ALT, ALP) biochemical parameters. No significant adverse effects on renal function were observed across the tested doses (IC\n                    <jats:sub>50<\/jats:sub>\n                    , IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009\u00d7\u20092, and IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009\u00d7\u20093). While AST and ALT levels remained stable, ALP levels showed a dose\u2010dependent modulation. These findings highlight the potential of\n                    <jats:bold>3g<\/jats:bold>\n                    as a promising anticancer agent for glioblastoma, warranting further investigation into its detailed mechanisms of action and long\u2010term safety.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70241","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:39:14Z","timestamp":1776422354000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis and Evaluation of Anticancer Potential of Novel Pyrrolopyrazines Against Glioblastoma: Mechanistic Details and In Vivo Safety Analysis"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5522-3469","authenticated-orcid":false,"given":"Ay\u015fe","family":"Usta","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science Van Y\u00fcz\u00fcnc\u00fc Yil University Van T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-7177","authenticated-orcid":false,"given":"Burak","family":"Kuzu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Van Y\u00fcz\u00fcnc\u00fc Yil University Van T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meltem","family":"Tan\u2010Uygun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Van Y\u00fcz\u00fcnc\u00fc Yil University Van T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-4989","authenticated-orcid":false,"given":"Veysel","family":"Y\u00fcksek","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, \u00d6zalp Vocational High School Van Y\u00fcz\u00fcnc\u00fc Y\u0131l University Van T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Edip Akyol","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine Van Y\u00fcz\u00fcnc\u00fc Y\u0131l University Van T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurettin","family":"Menges","sequence":"additional","affiliation":[{"name":"Scientific Research and Application Center (BITAM) Necmettin Erbakan University Konya T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.2017.025536"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21613"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.05.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1188\/16.CJON.S1.2-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2011.09.005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30020106"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol28040220"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2016.04.007"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.01036"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma11050779"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241060-00002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1179\/1743132815Y.0000000042"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2010.05.036"},{"issue":"3","key":"e_1_2_9_15_1","article-title":"Chemotherapy Wafers for High Grade Glioma","volume":"2011","author":"Hart M. 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