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Isoalantolactone/hydroxamic acid hybrids as potent dual STAT3/HDAC inhibitors and self-assembled nanoparticles for cancer therapy.
Mo, Hualong; Liu, JieYing; Su, Zhengxi; Zhao, Deng-Gao; Ma, Yan-Yan; Zhang, Kun; Wang, Qi; Fu, Chun; Wang, Yao; Chen, Meiwan; Hu, Burong.
Afiliación
  • Mo H; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
  • Liu J; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
  • Su Z; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
  • Zhao DG; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China. Electronic address: zhaodenggao@wyu.edu.cn.
  • Ma YY; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China. Electronic address: j002293@wyu.edu.cn.
  • Zhang K; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
  • Wang Q; Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China.
  • Fu C; Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China.
  • Wang Y; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
  • Chen M; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, China.
  • Hu B; Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China. Electronic address: brhu@wmu.edu.cn.
Eur J Med Chem ; 277: 116765, 2024 Nov 05.
Article en En | MEDLINE | ID: mdl-39146833
ABSTRACT
Conventional chemotherapy, especially with natural anticancer drugs, usually suffers from poor bioavailability and low tumor accumulation. To address these limitations, we developed a novel approach for modifying natural products in which amphiphilic hydroxamic acid hybrids based on a natural product isoalantolactone (IAL) were rationally designed. Compound 18 is identified as a highly potent dual signal transducer and activator of transcription 3 (STAT3)/histone deacetylases (HDAC) inhibitor and induces autophagy and apoptosis. 18 exhibits higher antitumor potency than IAL and the hydroxamic acid SAHA in vitro and in vivo. Furthermore, 18 self-assembled in water to form nanoparticles (18 NPs), which facilitated the accumulation of drugs in tumor tissues and promoted their cellular uptake, resulting in superior anticancer efficacy compared to free 18. Compared to drug-drug conjugates, hydroxamic acid hybrids have a smaller molecular weight and can synergize with various anticancer drugs. Overall, these findings indicate that 18 utilizing nanomedicines and dual-target drugs provide an efficient strategy for the rational design of dual-target drugs and the modification of natural products.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Apoptosis / Factor de Transcripción STAT3 / Nanopartículas / Inhibidores de Histona Desacetilasas / Ácidos Hidroxámicos / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Apoptosis / Factor de Transcripción STAT3 / Nanopartículas / Inhibidores de Histona Desacetilasas / Ácidos Hidroxámicos / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia