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An Insight into Medicinal Chemistry of Anticancer Drugs

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

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 27811

Special Issue Editors


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Guest Editor
Unidad Multidisciplinaria de Investigación Experimental Zaragoza, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México 09230, Mexico
Interests: drug repurposing in cancer research; pharmacogenetics; medicinal chemistry

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Guest Editor
Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico
Interests: natural products; therapeutic properties; skin cancer; neurosciences
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Special Issue Information

Dear Colleagues,

Cancer is one of the most common causes of death worldwide, making it a serious threat to the well-being and lives of people. Likewise, current treatments have diverse limitations, including unwanted side effects and resistance development. Therefore, the multifactorial and complex nature of cancer represents a global challenge to human health, requiring a comprehensive understanding of the underlying mechanisms and investigations of innovative therapeutic strategies.

This Special Issue welcomes original research and reviews articles covering distinct aspects of cancer research from different perspectives, including but not limited to the mechanisms of action of antitumor drugs, novel treatments, the relationship between chemical structure and antitumor agents' biological activity, cancer immunotherapy, polypharmacology, drug resistance, and multitargeted therapy. We are confident this Special Issue will be a valuable resource for students, researchers, and practitioners in medicine, pharmacology, and related health sciences.

Prof. Dr. Gabriela Figueroa-González
Dr. Hernán Cortés
Guest Editors

Manuscript Submission Information

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Keywords

  • natural products
  • anticancer
  • synthesis
  • drug resistance
  • multitargeted therapy

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Published Papers (2 papers)

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Research

15 pages, 2489 KB  
Article
Synthesis and Anti-Tumor Evaluation of Carboranyl BMS-202 Analogues—A Case of Carborane Not as Phenyl Ring Mimetic
by Changxian Yuan, Chaofan Li, Chenyang Ma, Yuzhe Lin, Linyuan Wang, Guanxiang Hao, Yirong Zhang, Hongjing Li, Yuan Li, Yu Zhao, Nan Sun, Tiezheng Chen, Zhiguang Zhang, Dengfeng Cheng and Sinan Wang
Molecules 2025, 30(24), 4789; https://doi.org/10.3390/molecules30244789 - 16 Dec 2025
Cited by 1 | Viewed by 777
Abstract
Carborane is considered a three-dimensional mimetic of phenyl rings in medicinal chemistry. BMS-202 is a potent PD-L1 inhibitor that can block the PD-L1/PD-1 interaction and restore the immune response to cancer cells. Herein, we replaced the terminal phenyl group of BMS-202 with carborane [...] Read more.
Carborane is considered a three-dimensional mimetic of phenyl rings in medicinal chemistry. BMS-202 is a potent PD-L1 inhibitor that can block the PD-L1/PD-1 interaction and restore the immune response to cancer cells. Herein, we replaced the terminal phenyl group of BMS-202 with carborane and prepared its carboranyl BMS-202 analogues. The results showed a loss of PD-L1 binding affinity due to the bulky size of carborane, suggesting that carborane cannot serve as a phenyl ring mimetic in certain cases. Docking study demonstrated that the narrow binding pocket of PD-L1 could not hold the bulky carborane, resulting in loss of its activity. Compounds 1a and 1b exhibited anti-proliferative activities on a broad scope of cancer cell lines. Further studies indicate that compound 1a can induce cell apoptosis and lead to G1 cell cycle phase arrest. The boron biodistribution study of compound 1a revealed that the brain/blood uptake ratio was 0.60 ± 0.08, exhibiting a good blood-brain penetration capability. Full article
(This article belongs to the Special Issue An Insight into Medicinal Chemistry of Anticancer Drugs)
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17 pages, 3323 KB  
Article
Fenbendazole Exhibits Antitumor Activity Against Cervical Cancer Through Dual Targeting of Cancer Cells and Cancer Stem Cells: Evidence from In Vitro and In Vivo Models
by Xi Lei, Yi Wang, Yuanyuan Chen, Jinyue Duan, Xin Gao and Zhongyi Cong
Molecules 2025, 30(11), 2377; https://doi.org/10.3390/molecules30112377 - 29 May 2025
Cited by 2 | Viewed by 26369
Abstract
Cervical cancer remains a major threat to women’s health, with advanced cases often exhibiting recurrence and metastasis due to cancer stem cells driving therapy resistance. This study evaluated fenbendazole (FBZ), a repurposed veterinary anthelmintic, for its antitumor activity dual targeting cervical cancer cells [...] Read more.
Cervical cancer remains a major threat to women’s health, with advanced cases often exhibiting recurrence and metastasis due to cancer stem cells driving therapy resistance. This study evaluated fenbendazole (FBZ), a repurposed veterinary anthelmintic, for its antitumor activity dual targeting cervical cancer cells (CCCs) and cervical cancer stem cells (CCSCs). CD133+CD44+ CCSCs were isolated from HeLa and C-33 A cell lines via immunomagnetic sorting and validated for stemness. Cell proliferation, cell cycle and apoptosis, and protein expression were detected by MST assay, flow cytometry, and Western blot analysis, respectively. FBZ dose-dependently inhibited proliferation, induced G2/M arrest, and triggered apoptosis in both CCCs and CCSCs. Mechanistically, FBZ upregulated cyclin B1 and phosphorylation of cdc25C-Ser198, while downregulating Wee1, phosphorylation of CDK1, and phosphorylation of cdc25C-Ser216, collectively enforcing G2/M blockade. In vivo, FBZ (100 mg/kg) significantly suppressed tumor growth in xenograft models without weight loss, contrasting with cisplatin-induced toxicity. Survival analysis revealed 100% survival in FBZ-treated mice versus 40% in cisplatin and 0% in untreated controls. These findings demonstrate FBZ’s unique ability to simultaneously target bulk tumor cells and therapy-resistant CCSCs via cell cycle disruption, supported by its preclinical safety and efficacy, positioning it as a promising therapeutic candidate for cervical cancer. Full article
(This article belongs to the Special Issue An Insight into Medicinal Chemistry of Anticancer Drugs)
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