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Synthesis of Anticancer Agents for Targeted Therapy

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

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2735

Special Issue Editor


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Guest Editor
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland
Interests: pharmaceuticals; drug synthesis; mass spectrometry; chromatography; QSPR; QSAR
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Special Issue Information

Dear Colleagues,

Molecularly targeted therapy is the latest cancer treatment. It involves finding a so-called molecular target, a feature or process in the tumor which can be activated to destroy or limit the growth of cancer cells. This target is determined for a specific cancer in a specific patient, making the treatment more effective and less harmful to healthy cells than, for example, standard chemotherapy. During targeted therapy, treatment focuses on destroying the disease and reducing the risk of nuisance side effects. Currently, a number of compounds are known to act selectively on various cancer cells, inhibiting molecular pathways in the process of oncogenesis by delivering drugs directly to cancer cells. The drugs used in targeted therapy act selectively, for example, on receptors for growth factors and dividing cells, antigens formed when genes are mutated in cancer cells, proteins responsible for the induction of apoptosis, and proteins that regulate the cell cycle and inhibit angiogenesis near the tumor.

In this Special Issue of the Molecules, we would like to focus on the design, synthesis, structural analysis, and study of the mechanisms of action of new chemical compounds that fit into the strategy of targeted therapy. We invite submissions of original research articles and comprehensive reviews covering a wide range of topics related to the discovery of new anticancer substances with potential for use in targeted therapy, including drug design, structure–activity relationship (SAR) studies, innovative synthetic strategies, and evaluation of the anticancer activity of new substances and explanation of the molecular mechanisms underlying their anticancer activity.

Dr. Małgorzata Jeleń
Guest Editor

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Keywords

  • organic synthesis of anticancer compounds
  • targeted cancer therapy
  • medicinal chemistry
  • structure–activity relationship (SAR)
  • molecular-targeted therapy
  • drug development
  • chemotherapeutic agents
  • cell signaling pathways
  • monoclonal antibody
  • cancer-altered pathway

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Published Papers (3 papers)

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Research

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21 pages, 3491 KB  
Article
Phosphoramidate Derivatives of Betulin, New Molecules with Promising Biological Activity: Synthesis and Characterization
by Elwira Chrobak, Marta Świtalska, Marcel Madej, Joanna Wietrzyk and Ewa Bębenek
Molecules 2026, 31(6), 935; https://doi.org/10.3390/molecules31060935 - 11 Mar 2026
Viewed by 532
Abstract
Studies of natural products and their semisynthetic derivatives are a valuable source of therapeutic agents. The aim of this work was to obtain new 30-phosphoramidate derivatives of betulin and determine their biological potential. The synthetic approach utilized the Staudinger reaction (the introduction of [...] Read more.
Studies of natural products and their semisynthetic derivatives are a valuable source of therapeutic agents. The aim of this work was to obtain new 30-phosphoramidate derivatives of betulin and determine their biological potential. The synthetic approach utilized the Staudinger reaction (the introduction of a phosphoramidate group), the Steglich reaction (the introduction of an alkynyl group), and the Jones reaction (the introduction of a carboxyl group). The structures of the target compounds were determined using spectroscopic methods (1H NMR, 13C NMR, 31P NMR, and HRMS). The new derivatives were tested for antiproliferative activity against MV4-11, A549, MCF-7, PC-3, and HCT116 cancer cells and against normal MCF-10A cells using the MTT and SRB methods. Apoptosis studies were performed for the most active compounds (6B and 7A), potential molecular targets (AutoDock software) were identified, and lipophilicity parameters (RP-TLC method, SwissADME website) were determined. The greatest effect on apoptosis and caspase 3/7 activation was observed for the diester derivative 7A. Compound 7A showed a high lipophilicity parameter in the study group. Full article
(This article belongs to the Special Issue Synthesis of Anticancer Agents for Targeted Therapy)
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14 pages, 1971 KB  
Article
Synthesis and In Vitro Evaluation of Anticancer Activity of Fluorophenyl Derivatives of 1,3,4-Thiadiazole Against Estrogen-Dependent Breast Cancer
by Sara Janowska, Anna Makuch-Kocka, Rafał Kurczab, Oleg M. Demchuk and Monika Wujec
Molecules 2025, 30(24), 4744; https://doi.org/10.3390/molecules30244744 - 12 Dec 2025
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Abstract
Breast cancer remains the most frequently diagnosed malignant tumor among women worldwide, and the limited selectivity as well as the emerging resistance to currently used therapies highlight the need to search for new therapeutic compounds. Aromatase, a key enzyme in the estrogen biosynthesis [...] Read more.
Breast cancer remains the most frequently diagnosed malignant tumor among women worldwide, and the limited selectivity as well as the emerging resistance to currently used therapies highlight the need to search for new therapeutic compounds. Aromatase, a key enzyme in the estrogen biosynthesis pathway, represents a recognized molecular target in the treatment of hormone-dependent cancers. In this study, six new 1,3,4-thiadiazole derivatives containing two halogen-substituted aromatic rings were designed and synthesized as potential nonsteroidal aromatase inhibitors. The cytotoxic activity of the obtained compounds was evaluated against two breast cancer cell lines: MCF-7 (estrogen-dependent) and MDA-MB-231 (estrogen-independent). All tested compounds exhibited concentration-dependent cytotoxic activity against MCF-7 cells, with the strongest effects observed for compounds A2, A3, B1, and B3 (IC50 ≈ 52–55 µM). In contrast, none of the tested compounds showed significant activity against MDA-MB-231 cells (IC50 > 100 µM), suggesting their selectivity toward estrogen-dependent cancer cells. Compound B3, identified as the most promising, was further subjected to in silico analyses. Molecular docking and molecular dynamics simulations revealed that B3 occupies a binding site similar to that of the co-crystallized native inhibitor and forms interactions characteristic of strong aromatase inhibitors. The obtained results confirm a mechanism of action related to aromatase inhibition and indicate that fluorophenyl-substituted 1,3,4-thiadiazole derivatives represent a promising scaffold for the design of new, selective, and less toxic aromatase inhibitors. Full article
(This article belongs to the Special Issue Synthesis of Anticancer Agents for Targeted Therapy)
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Review

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92 pages, 3288 KB  
Review
Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies
by Klaudia Giercuszkiewicz-Haśnik, Beata Morak-Młodawska and Małgorzata Jeleń
Molecules 2026, 31(7), 1195; https://doi.org/10.3390/molecules31071195 - 3 Apr 2026
Viewed by 672
Abstract
Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We [...] Read more.
Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase (PARP) inhibition, and epigenetic or metabolic targets including histone deacetylases (HDACs), bromodomain and extra-terminal proteins (BET), and mutant isocitrate dehydrogenases (IDH1/2). Across these areas, we summarize recurrent resistance mechanisms and the rationale for combination or sequential approaches. Biologic targeted therapy is discussed in parallel, including immune checkpoint blockade, antibody–drug conjugates, bispecific antibodies (BsAb), and cell therapies such as chimeric antigen receptor T cells, with emphasis on biomarker-guided patient stratification. Finally, we outline emerging directions beyond canonical nodes, including modulation of the p53-MDM2/MDM4 axis, ferroptosis control through AIFM2/FSP1, and innate immune pathways such as CD47-SIRPa and the stimulator of interferon genes (STING). Overall, the field is shifting from single-target inhibition toward integrated strategies that combine precise molecular targeting with an understanding of signaling network dynamics, resistance evolution, and therapeutic vulnerabilities. Full article
(This article belongs to the Special Issue Synthesis of Anticancer Agents for Targeted Therapy)
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