{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T22:51:37Z","timestamp":1782600697220,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T00:00:00Z","timestamp":1455840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Northeast Ohio Medical University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Preclinical studies for neurodegenerative diseases have shown a multi\u2010targeted approach to be successful in the treatment of these complex disorders with several pathoetiological pathways. Polycyclic compounds, such as NGP1\u201001 (<jats:bold>7a<\/jats:bold>), have demonstrated the ability to target multiple mechanisms of the complex etiology and are referred to as multifunctional compounds. These compounds have served as scaffolds with the ability to attenuate Ca<jats:sup>2+<\/jats:sup>overload and excitotoxicity through several pathways. In this study, our focus was on mitigating Ca<jats:sup>2+<\/jats:sup>overload through the L\u2010type calcium channels (LTCC). Here, we report the synthesis and biological evaluation of several novel polycyclic compounds. We determined the IC<jats:sub>50<\/jats:sub>values for both the pentacycloundecylamines and the triquinylamines by means of a high\u2010throughput fluorescence calcium flux assay utilizing Fura\u20102\/AM. The potential of these compounds to offer protection against hydrogen peroxide\u2010induced cell death was also evaluated. Overall, 8\u2010benzylamino\u20108,11\u2010oxapentacyclo[5.4.0.0<jats:sup>2,6<\/jats:sup>.0<jats:sup>3,10<\/jats:sup>.0<jats:sup>5,9<\/jats:sup>]undecane (NGP1\u201001,<jats:bold>7a<\/jats:bold>) had the most favorable pharmacological profile with an IC<jats:sub>50<\/jats:sub>value of 86\u2009\u00b5M for LTCC inhibition and significant reduction of hydrogen peroxide\u2010induced cell death. In general, the triquinylamines were more active as LTCC blockers than the oxa\u2010pentacycloundecylamines. The aza\u2010pentacycloundecylamines were potent LTCC inhibitors, with 8\u2010hydroxy\u2010<jats:italic>N<\/jats:italic>\u2010phenylethyl\u20108,11\u2010azapentacyclo[5.4.0.0<jats:sup>2,6<\/jats:sup>.0<jats:sup>3,10<\/jats:sup>.0<jats:sup>5,9<\/jats:sup>]undecane (<jats:bold>8b<\/jats:bold>) also able to offer significant protection in the cell viability assays.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ardp.201500293","type":"journal-article","created":{"date-parts":[[2016,2,20]],"date-time":"2016-02-20T14:12:17Z","timestamp":1455977537000},"page":"252-267","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis and Biological Evaluation of Pentacycloundecylamines and Triquinylamines as Voltage\u2010Gated Calcium Channel Blockers"],"prefix":"10.1002","volume":"349","author":[{"given":"Lois\u2010May","family":"Young","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University Rootstown OH USA"},{"name":"Pharmaceutical Chemistry, School of Pharmacy North\u2010West University Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner J.","family":"Geldenhuys","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University Rootstown OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olwen C.","family":"Domingo","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, School of Pharmacy North\u2010West University Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarel F.","family":"Malan","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, School of Pharmacy North\u2010West University Potchefstroom South Africa"},{"name":"School of Pharmacy University of the Western Cape Bellville South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis J.","family":"Van der Schyf","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University Rootstown OH USA"},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy Idaho State University Pocatello ID USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb44398.x"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02621"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(95)90006-3"},{"key":"e_1_2_8_2_4","first-page":"575","volume":"60","author":"Wojda U.","year":"2008","journal-title":"Life"},{"key":"e_1_2_8_2_5","doi-asserted-by":"publisher","DOI":"10.1007\/s001090000077"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(03)00141-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161206775474503"},{"key":"e_1_2_8_5_1","first-page":"16","volume":"17","author":"Inzitari D.","year":"2006","journal-title":"Aging Clin. 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