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.

1,2,3-triazole-containing drug click reaction drug discovery hepatocellular carcinoma (HCC) selective anti-HepG2 agent sorafenib analog targeted cancer drug

Journal

Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453

Informations de publication

Date de publication:
20 Apr 2022
Historique:
received: 24 02 2022
revised: 15 04 2022
accepted: 16 04 2022
entrez: 28 5 2022
pubmed: 29 5 2022
medline: 29 5 2022
Statut: epublish

Résumé

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,

Identifiants

pubmed: 35631331
pii: ph15050504
doi: 10.3390/ph15050504
pmc: PMC9147274
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Thailand Research Fund
ID : MRG6180105
Organisme : Thailand Research Fund
ID : RTA6280004

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Auteurs

Sittisak Oekchuae (S)

Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand.
Chulabhorn Research Institute, Bangkok 10210, Thailand.

Jitnapa Sirirak (J)

Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand.

Purin Charoensuksai (P)

Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.

Pawaris Wongprayoon (P)

Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.

Natthaya Chuaypen (N)

Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Jutatip Boonsombat (J)

Chulabhorn Research Institute, Bangkok 10210, Thailand.
Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok 10400, Thailand.

Somsak Ruchirawat (S)

Chulabhorn Research Institute, Bangkok 10210, Thailand.
Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok 10400, Thailand.
Program in Chemical Sciences, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand.

Pisit Tangkijvanich (P)

Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Apichart Suksamrarn (A)

Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.

Panupun Limpachayaporn (P)

Department of Chemistry, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand.

Classifications MeSH