دورية أكاديمية
Synthesis and anti-proliferative effect of novel 4-Aryl-1, 3-Thiazole-TPP conjugates via mitochondrial uncoupling process.
| العنوان: | Synthesis and anti-proliferative effect of novel 4-Aryl-1, 3-Thiazole-TPP conjugates via mitochondrial uncoupling process. |
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| المؤلفون: | Hu Y; Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China., Zhang Y; Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China., Guo J; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Chen S; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Jin J; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Li P; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Pan Y; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Lei S; Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China., Li J; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Wu S; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Bu B; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China., Fu L; Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China. Electronic address: lei.fu@xjtlu.edu.cn. |
| المصدر: | Bioorganic chemistry [Bioorg Chem] 2024 Sep; Vol. 150, pp. 107588. Date of Electronic Publication: 2024 Jun 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| مواضيع طبية MeSH: | Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemical synthesis , Antineoplastic Agents*/chemistry , Cell Proliferation*/drug effects , Mitochondria*/drug effects , Mitochondria*/metabolism , Drug Screening Assays, Antitumor* , Thiazoles*/pharmacology , Thiazoles*/chemistry , Thiazoles*/chemical synthesis , Membrane Potential, Mitochondrial*/drug effects , Apoptosis*/drug effects , Dose-Response Relationship, Drug* , Reactive Oxygen Species*/metabolism, Humans ; Structure-Activity Relationship ; Molecular Structure ; Cell Line, Tumor ; Organophosphorus Compounds/pharmacology ; Organophosphorus Compounds/chemistry ; Organophosphorus Compounds/chemical synthesis |
| مستخلص: | With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP + ), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP + moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Anticancer; Mitochondrial bioenergetics; Mitochondrial targeting; Mitochondrial uncoupler; Oxidative phosphorylation |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Thiazoles) 0 (Reactive Oxygen Species) 0 (Organophosphorus Compounds) |
| تواريخ الأحداث: | Date Created: 20240627 Date Completed: 20240719 Latest Revision: 20240722 |
| رمز التحديث: | 20240722 |
| DOI: | 10.1016/j.bioorg.2024.107588 |
| PMID: | 38936051 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2024.107588 |