{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:20:05Z","timestamp":1779891605085,"version":"3.53.1"},"reference-count":96,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["MRG6180105"],"award-info":[{"award-number":["MRG6180105"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["RTA6280004"],"award-info":[{"award-number":["RTA6280004"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Target cancer drug therapy is an alternative treatment for advanced hepatocellular carcinoma (HCC) patients. However, the treatment using approved targeted drugs has encountered a number of limitations, including the poor pharmacological properties of drugs, therapy efficiency, adverse effects, and drug resistance. As a consequence, the discovery and development of anti-HCC drug structures are therefore still in high demand. Herein, we designed and synthesized a new series of 1,2,3-triazole-cored structures incorporating aryl urea as anti-HepG2 agents. Forty-nine analogs were prepared via nucleophilic addition and copper-catalyzed azide-alkyne cycloaddition (CuAAC) with excellent yields. Significantly, almost all triazole-cored analogs exhibited less cytotoxicity toward normal cells, human embryonal lung fibroblast cell MRC-5, compared to Sorafenib and Doxorubicin. Among them, 2m\u2019 and 2e exhibited the highest selectivity indexes (SI = 14.7 and 12.2), which were ca. 4.4- and 3.7-fold superior to that of Sorafenib (SI = 3.30) and ca. 3.8- and 3.2-fold superior to that of Doxorubicin (SI = 3.83), respectively. Additionally, excellent inhibitory activity against hepatocellular carcinoma HepG2, comparable to Sorafenib, was still maintained. A cell-cycle analysis and apoptosis induction study suggested that 2m\u2019 and 2e likely share a similar mechanism of action to Sorafenib. Furthermore, compounds 2m\u2019 and 2e exhibit appropriate drug-likeness, analyzed by SwissADME. With their excellent anti-HepG2 activity, improved selectivity indexes, and appropriate druggability, the triazole-cored analogs 2m\u2019 and 2e are suggested to be promising candidates for development as targeted cancer agents and drugs used in combination therapy for the treatment of HCC.<\/jats:p>","DOI":"10.3390\/ph15050504","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T03:46:11Z","timestamp":1650512771000},"page":"504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Design and Synthesis of a New Series of 1,2,3-Triazole-Cored Structures Tethering Aryl Urea and Their Highly Selective Cytotoxicity toward HepG2"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5940-4910","authenticated-orcid":false,"given":"Sittisak","family":"Oekchuae","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand"},{"name":"Chulabhorn Research Institute, Bangkok 10210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitnapa","family":"Sirirak","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purin","family":"Charoensuksai","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawaris","family":"Wongprayoon","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natthaya","family":"Chuaypen","sequence":"additional","affiliation":[{"name":"Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutatip","family":"Boonsombat","sequence":"additional","affiliation":[{"name":"Chulabhorn Research Institute, Bangkok 10210, Thailand"},{"name":"Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somsak","family":"Ruchirawat","sequence":"additional","affiliation":[{"name":"Chulabhorn Research Institute, Bangkok 10210, Thailand"},{"name":"Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok 10400, Thailand"},{"name":"Program in Chemical Sciences, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-8671","authenticated-orcid":false,"given":"Pisit","family":"Tangkijvanich","sequence":"additional","affiliation":[{"name":"Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8919-3555","authenticated-orcid":false,"given":"Apichart","family":"Suksamrarn","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7903-4980","authenticated-orcid":false,"given":"Panupun","family":"Limpachayaporn","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021, July 27). 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