دورية أكاديمية
Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer.
| العنوان: | Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer. |
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| المؤلفون: | Liang Q; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China., Zhang S; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China., Liu J; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China., Zhou X; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China; Department of Pharmacology and Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor., Syamimi Ariffin N; Department of Pharmacology and Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor., Wei J; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China., Shi C; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China., Ma X; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China. Electronic address: mxl78@glmc.edu.cn., Zhang Y; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China. Electronic address: zhangye81@126.com., Huang R; Guangxi Key Laboratory of Drug Discovery and Optimization, Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, School of Pharmacy, Guilin Medical University, Guilin 541199, China. Electronic address: rzhuang1783@163.com. |
| المصدر: | Bioorganic chemistry [Bioorg Chem] 2024 Sep; Vol. 150, pp. 107596. Date of Electronic Publication: 2024 Jun 26. |
| 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: | Carbonic Anhydrase IX*/antagonists & inhibitors , Carbonic Anhydrase IX*/metabolism , Triple Negative Breast Neoplasms*/drug therapy , Triple Negative Breast Neoplasms*/pathology , Triple Negative Breast Neoplasms*/metabolism , Carbonic Anhydrase Inhibitors*/pharmacology , Carbonic Anhydrase Inhibitors*/chemistry , Carbonic Anhydrase Inhibitors*/chemical synthesis , Ferroptosis*/drug effects , Sulfonamides*/pharmacology , Sulfonamides*/chemistry , Sulfonamides*/chemical synthesis , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/chemical synthesis , Benzenesulfonamides* , Drug Screening Assays, Antitumor* , Cell Proliferation*/drug effects , Dose-Response Relationship, Drug* , Naphthalimides*/chemistry , Naphthalimides*/pharmacology , Naphthalimides*/chemical synthesis, Humans ; Animals ; Molecular Structure ; Structure-Activity Relationship ; Mice ; Female ; Drug Discovery ; Apoptosis/drug effects ; Molecular Docking Simulation ; Piperazines/pharmacology ; Piperazines/chemistry ; Piperazines/chemical synthesis ; Cell Line, Tumor ; Antigens, Neoplasm |
| مستخلص: | A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC. 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: 1,8-Naphthalimide; Benzenesulfonamide; Carbonic anhydrase IX inhibitors; Ferroptosis; Triple-negative breast cancer |
| المشرفين على المادة: | EC 4.2.1.1 (Carbonic Anhydrase IX) 0 (Carbonic Anhydrase Inhibitors) 0 (Sulfonamides) 0 (Antineoplastic Agents) 0 (Benzenesulfonamides) 0 (Naphthalimides) EC 4.2.1.1 (CA9 protein, human) 0 (Piperazines) 0 (Antigens, Neoplasm) |
| تواريخ الأحداث: | Date Created: 20240628 Date Completed: 20240719 Latest Revision: 20240722 |
| رمز التحديث: | 20240722 |
| DOI: | 10.1016/j.bioorg.2024.107596 |
| PMID: | 38941699 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2024.107596 |