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  3. Synthesis and biological evaluation of novel isatin-phenol hybrids as potential antitumor agents

Synthesis and biological evaluation of novel isatin-phenol hybrids as potential antitumor agents

  • Bioorg Chem. 2025 Jan 31:157:108232. doi: 10.1016/j.bioorg.2025.108232.
Zhi Chen 1,  Yishan Guo 1,  Yuwei Peng 1,  Xiaojun Tan 1,  Haoxiong Chen 1,  Daqiang Luo 1,  Kaixuan Luo 1,  Dudu Wu 1,  Zunnan Huang 2,  Zhiqiang Yu 3,  Cheng Tao 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Natural Drugs Research and Development, The First Dongguan Affiliated Hospital and School of Pharmacy, Guangdong Medical University, Dongguan 523808, China.
  • 2 Guangdong Provincial Key Laboratory of Natural Drugs Research and Development, The First Dongguan Affiliated Hospital and School of Pharmacy, Guangdong Medical University, Dongguan 523808, China; Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer‑Aided Drug Design of Dongguan City, Guangdong Medical University, Dongguan 523808, China. Electronic address: zn_huang@gdmu.edu.cn.
  • 3 Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, China. Electronic address: yuzq@smu.edu.cn.
  • 4 Guangdong Provincial Key Laboratory of Natural Drugs Research and Development, The First Dongguan Affiliated Hospital and School of Pharmacy, Guangdong Medical University, Dongguan 523808, China. Electronic address: taocheng@gdmu.edu.cn.
PMID: 39919326 DOI: 10.1016/j.bioorg.2025.108232
Abstract

Chemotherapy was one of indispensable methods for treating Cancer, and the development of novel antitumor drugs was necessary due to the emergent drug resistance and undesirable side effects. In the current study, we successfully constructed a novel library of isatin-phenol hybrids by chemical coupling of isatin (1) with a series of active Phenols including honokiol (2), magnolol (3), bis(4-hydroxy-3-methylphenyl) sulfide (4), bisphenol A (5), carvacrol (6), and hydroxyqunioline (7) respectively. The target molecules were screened for Anticancer activity, and we further investigate the anti-cancer mechanism of the most potent compound IPH10 in vitro and in vivo. Animal experiments demonstrated that IPH10 possessed strong anti-tumor effects in vivo without hepatic and renal toxicity. Moreover, the effects of IPH10 on mitochondrial membrane potential (JC-1) and Reactive Oxygen Species (ROS) in tumor cells were investigated, and the results showed that IPH10 could significantly increase the content of ROS and dramatically decrease the mitochondrial membrane potential in tumor cells. Furthermore, the effect of IPH10 on apoptotic proteins in tumor cells was also explored by Western blotting analysis, which revealed that IPH10 could significantly increase the protein content of cleaved caspase-9/cleaved Caspase-3/cleaved caspase-7/cleaved PARP. Taken together, the current study reported a promising novel chemotherapeutic drug candidate IPH10 that could inhibit the growth and induce the Apoptosis of tumor cells.

Keywords

Antitumor; Apoptosis; Hybrid; Isatin; Magnolol.

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