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Design, Synthesis and Biological Activity of Novel Antitumor Drugs, 2nd Edition

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 April 2026) | Viewed by 986

Special Issue Editors


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Guest Editor
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Salerno, Italy
Interests: design, synthesis and biological characterization of pharmacologically actives small molecules, peptidomimetics e peptides (antitumoral agents, antiviral compounds and ionic channel modulators); study of new reaction mechanisms and synthetic strategy optimization
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Salerno, Italy
Interests: novel target; anticancer; small molecules; biological evaluation; synthesis; activity assay; molecular modeling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Anticancer therapy represents an open challenge in the research field due to off-target toxicity and the development of chemoresistance phenomena. The recent advances in molecular biology have opened the way for the recognition of novel molecular targets that previously have not been explored and analyzed for cancer treatment. In this context, a design that is supported by molecular modeling methodologies, synthesis, and the pharmacological characterization of small molecules active against these new targets plays a key role in the medicinal chemistry field, representing a focal point for the future development of more effective treatments.

Dr. Alessia Bertamino
Dr. Tania Ciaglia
Guest Editors

Manuscript Submission Information

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Keywords

  • novel target
  • anticancer
  • small molecules
  • biological evaluation
  • synthesis
  • activity assay
  • molecular modeling

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Published Papers (1 paper)

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Research

20 pages, 5769 KB  
Article
A Novel Wogonin Derivative Induces Apoptosis in PC-3M Cells by Targeting Mitochondrial Dysfunction and Activating the ROS-p38/MAPK Pathway
by Dingrui Liu, Fangfei Liu, Mingjie Song, Fengyan Su, Wei Li, Yan Zhao, Jiahong Han and Enbo Cai
Molecules 2026, 31(5), 859; https://doi.org/10.3390/molecules31050859 - 5 Mar 2026
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Abstract
Current cancer treatments have significant limitations. Designing TPP+-modified, mitochondrial-targeted drugs can improve anticancer efficacy. Although wogonin exhibits antitumor activity, it has drawbacks, including poor solubility and limited distribution. This study designed and synthesized 27 derivatives, including nine novel wogonin triphenylphosphine derivatives [...] Read more.
Current cancer treatments have significant limitations. Designing TPP+-modified, mitochondrial-targeted drugs can improve anticancer efficacy. Although wogonin exhibits antitumor activity, it has drawbacks, including poor solubility and limited distribution. This study designed and synthesized 27 derivatives, including nine novel wogonin triphenylphosphine derivatives that demonstrated in vitro antitumor activity. Mito-WO-8, one of these derivatives, exhibited potent activity against PC-3M cells (IC50 = 3.19 μmol/L), demonstrating 15-fold higher potency than wogonin. Further analysis revealed that Mito-WO-8 accumulates more in mitochondria than wogonin and induces mitochondrial dysfunction, including increased reactive oxygen species, reduced membrane potential, and activation of the MPTP channel. Transcriptome and network analyses revealed that Mito-WO-8 activates the p38/MAPK pathway. Downregulation of p-MKK6 and p-p38, as well as upregulation of DDIT3 and cleaved caspase-3, were validated by Western blot (WB) and quantitative polymerase chain reaction (qPCR). Therefore, Mito-WO-8 enhances mitochondrial enrichment and induces mitochondrial damage. This process is associated with apoptosis and the activation of the ROS-p38/MAPK pathway. Additionally, the study found that Mito-WO-8 exhibits a stronger binding affinity for mitochondrial glycerol-3-phosphate dehydrogenase 2 (GPD2) than the parent compound (−9.6 kJ/mol vs. −6.6 kJ/mol), suggesting a potential interaction with GPD2. This finding establishes a foundation for further investigation into its targeted antitumor mechanism. Full article
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