{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:38:22Z","timestamp":1760236702468,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-MARC","award":["T34GM008048-35"],"award-info":[{"award-number":["T34GM008048-35"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicines"],"abstract":"<jats:p>A series of 3,5-bis(benzylidene)-4-piperidones 2a\u2013u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF) and human pulp cells (HPC), thereby demonstrating tumour-selective toxicity. A further study revealed that most of the compounds in series 2 were more toxic to the human Colo-205 adenocarcinoma cell line (Colo-205), human HT29 colorectal adenocarcinoma cells (HT-29) and human CEM lymphoid cells (CEM) neoplasms than towards non-malignant human foreskin Hs27 fibroblast line (Hs27) cells. The potency of the cytotoxins towards the six malignant cell lines increased as the sigma and sigma star values of the aryl substituents rose. Attempts to condense various aryl aldehydes with 2,2,6,6-tetramethyl-4-piperidone led to the isolation of some 1,5-diaryl-1,4-pentadien-3-ones. The highest specificity for oral cancer cells was displayed by 2e and 2r. In the case of 2r, its selective toxicity exceeded that of doxorubicin and melphalan. The enones 2k, m, o have the highest SI values towards colon cancer and leukemic cells. Both 2e,r inhibited mitosis and increased the subG1 population (with a transient increase in G2\/M phase cells). Slight activation of caspase-3, based on the cleavage of poly(ADP-ribose)polymerase (PARP) and procaspase 3, was detected.<\/jats:p>","DOI":"10.3390\/medicines8120078","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T21:32:40Z","timestamp":1639690360000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3712-5790","authenticated-orcid":false,"given":"Praveen K.","family":"Roayapalley","sequence":"first","affiliation":[{"name":"Drug Discovery and Development Research Group, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8001-2121","authenticated-orcid":false,"given":"Hiroshi","family":"Sakagami","sequence":"additional","affiliation":[{"name":"School of Dentistry, Meikai University, Sakado, Saitama 350-0283, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keitaro","family":"Satoh","sequence":"additional","affiliation":[{"name":"School of Dentistry, Meikai University, Sakado, Saitama 350-0283, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Amano","sequence":"additional","affiliation":[{"name":"School of Dentistry, Meikai University, Sakado, Saitama 350-0283, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-3034","authenticated-orcid":false,"given":"Kenjiro","family":"Bandow","sequence":"additional","affiliation":[{"name":"School of Dentistry, Meikai University, Sakado, Saitama 350-0283, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato J.","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968-0519, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla G. Cano","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968-0519, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austre Y.","family":"Schiaffino Bustamante","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968-0519, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen G.","family":"Dimmock","sequence":"additional","affiliation":[{"name":"Department of Finance, National University of Singapore, Singapore 119245, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajendra K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umashankar","family":"Das","sequence":"additional","affiliation":[{"name":"Drug Discovery and Development Research Group, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan R.","family":"Dimmock","sequence":"additional","affiliation":[{"name":"Drug Discovery and Development Research Group, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejmech.2018.01.088","article-title":"Novel dissymmetric 3,5-bis(arylidene)-4-piperidones as potential antitumor agents with biological evaluation in vitro and in vivo","volume":"147","author":"Li","year":"2018","journal-title":"Eur. 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