{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:09:26Z","timestamp":1784171366445,"version":"3.55.0"},"reference-count":16,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A series of 2-(1H-indol-3-yl)-5-substituted-1,3,4-oxadiazoles, 4a\u2013m, were designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2 inhibitory anticancer agents based on our previously reported hit compounds. Synthesis of the target 1,3,4-oxadiazoles was readily accomplished through a cyclization reaction of indole carboxylic acid hydrazide 2 with substituted carboxylic acid derivatives 3a\u2013m in the presence of phosphorus oxychloride. New compounds 4a\u2013m showed a range of IC50 values concentrated in the low micromolar range selectively in Bcl-2 positive human cancer cell lines. The most potent candidate 4-trifluoromethyl substituted analogue 4j showed selective IC50 values of 0.52\u20130.88 \u03bcM against Bcl-2 expressing cell lines with no inhibitory effects in the Bcl-2 negative cell line. Moreover, 4j showed binding that was two-fold more potent than the positive control gossypol in the Bcl-2 ELISA binding affinity assay. Molecular modeling studies helped to further rationalize anti-apoptotic Bcl-2 binding and identified compound 4j as a candidate with drug-like properties for further investigation as a selective Bcl-2 inhibitory anticancer agent.<\/jats:p>","DOI":"10.3390\/ijms21238980","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T09:04:15Z","timestamp":1606381455000},"page":"8980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2"],"prefix":"10.3390","volume":"21","author":[{"given":"Rania","family":"Hamdy","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK"},{"name":"Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"},{"name":"Research Institute for Medical and Health Sciences, University of Sharjah, P.O. Box 27272, Sharjah, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0040-0288","authenticated-orcid":false,"given":"Samia A.","family":"Elseginy","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK"},{"name":"Green Chemistry Department, Chemical Industries Research Division, National Research Center, Cairo, Egypt"},{"name":"School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha I.","family":"Ziedan","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK"},{"name":"Department of Mathematical and Physical Sciences, University of Chester, Chester CH2 4NU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6038-1496","authenticated-orcid":false,"given":"Mohamed","family":"El-Sadek","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsaid","family":"Lashin","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-8905","authenticated-orcid":false,"given":"Arwyn T.","family":"Jones","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Westwell","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrd.2016.253","article-title":"From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors","volume":"16","author":"Ashkenazi","year":"2017","journal-title":"Nat. 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