Article
Chemistry, Multidisciplinary
Lingyan Liu, Feiyang Liu, Dongya Liu, Wei Yuan, Mengfan Zhang, Peng Wei, Tao Yi
Summary: The study developed a reactive oxygen species (ROS)-activated smart theranostic prodrug system for efficient regional chemotherapy of metastatic cancers. The optimized prodrug showed high sensitivity to ROS and specifically targeted cervical cancer cells, resulting in highly efficient drug release and strong toxicity towards cancer cells but not normal cells. This prodrug also displayed significantly enhanced antitumor efficacy in vivo with no obvious side effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Qiqiang Xie, Guangbin Dong
Summary: The Matteson-type reactions have gained increasing interest in organic synthesis, but current tactics mainly focus on carbon chains. In this study, we report the development of the oxa-Matteson reaction, which allows oxygen and carbenoid insertions into alkyl- and arylboronates, leading to the synthesis of boron-substituted ethers. The method demonstrates its utility in the preparation of functional ethers, asymmetric synthesis, and programmable construction of polyethers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Hichem Maslah, Charles Skarbek, Catherine Gourson, Marie-Aude Plamont, Stephanie Pethe, Ludovic Jullien, Thomas Le Saux, Raphael Labruere
Summary: A new platform capable of generating cytotoxic agents through intramolecular cyclization has been reported, showing rapid and effective action against cancer cells. This innovative method offers potential for prodrug development in anticancer therapy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Inorganic & Nuclear
Hulya Gizem Ozkan, Johannes Toms, Simone Maschauer, Olaf Prante, Andriy Mokhir
Summary: NAAF prodrugs are activated in the presence of ROS to target cancer cells, PET imaging is used to investigate their biodistribution in vivo, and a stable marker is needed to extend the observation window.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Review
Chemistry, Applied
Serena Pillitteri, Prabhat Ranjan, Erik V. Van der Eycken, Upendra K. Sharma
Summary: The chemistry of boron compounds has been extensively studied and applied in synthetic and biologically active molecules. The advent of photoredox catalysis has led to a surge in the discovery of suitable radical precursors, with boron playing a prominent role. However, the use of boronic acids and esters in photocatalyzed reactions has received less attention, and methods to enable their involvement have only recently been developed. Nonetheless, this review summarizes novel strategies to unlock their potential as radical precursors in photochemical reactions by exploiting their intrinsic chemical properties.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Inorganic & Nuclear
Hong-Gui Xu, Saparmyrat Annamadov, Andriy Mokhir
Summary: Ferrocene derivatives have potential anticancer activity, but their chemical stability remains a challenge. In this study, new 4-ferrocenylaniline-based prodrugs were developed, which showed improved stability and activity compared to previous ferrocene prodrugs. They exhibited anticancer activity through ROS generation.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Xiaonan Li, Donghui Cao, Siming Sun, Yuehui Wang
Summary: Dysregulation of reactive oxygen species (ROS) production and ROS-regulated pathways in cancer cells can have dual effects on cancer progression, either promoting transformation/proliferation or inducing cell death. Targeting ROS is a promising strategy for cancer treatment, and ginsenosides and related drug carriers have shown potential in modulating multiple signaling pathways to induce apoptosis, regulate cell cycle, invasion, and metastasis, and enhance drug sensitivity in different cancers. This review focuses on the pro- and anticancer effects of ROS and summarizes the mechanisms and recent advances in ginsenosides for anticancer therapy by targeting ROS, providing insights for future studies.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Prabhat Ranjan, Serena Pillitteri, Guglielmo Coppola, Monica Oliva, Erik V. Van der Eycken, Upendra K. Sharma
Summary: This study demonstrates the use of amide solvents to modulate the oxidation potential of boronic acids for alkyl radical generation in visible-light-assisted photocatalyzed reactions. The developed protocol is simple and applicable for various reactions, including the synthesis of unnatural amino acids. Furthermore, selective generation of radical species from boronic acids in the presence of boronic ester-containing molecules is now feasible, allowing for potential boron-selective modifications.
Article
Chemistry, Organic
Sofia A. G. Monteiro, Pedro M. P. Gois, Joao P. M. Antonio
Summary: Despite advances in cancer treatment, the low selectivity of chemotherapy to cancer cells has resulted in significant side effects. Therefore, the development of targeted alternatives that deliver cytotoxic payloads selectively to cancer cells has become necessary. Reactive oxygen species (ROS), despite being present in high concentrations in cancer cells, have been underexplored as a stimulus for targeted prodrugs. This review provides insights into the use of ROS-responsive prodrugs, discussing their mechanisms, applications, advantages, limitations, and future challenges.
Article
Chemistry, Multidisciplinary
Hulya Gizem Ozkan, Vanrajsinh Thakor, Hong-Gui Xu, Galyna Bila, Rostyslav Bilyy, Daria Bida, Martin Boettcher, Dimitrios Mougiakakos, Rainer Tietze, Andriy Mokhir
Summary: Elevated levels of reactive oxygen species (ROS) and deficient mitochondria are weak points of cancer cells. Designing highly potent anticancer drugs that target both ROS and mitochondria is a valid therapeutic strategy. However, limiting the drug effects to cancer cells without affecting normal ones remains a challenge. In this study, we developed novel aminoferrocene derivatives that are chemically stable in the presence of ROS, generate mitochondrial ROS in cancer cells but not normal cells, and exhibit anticancer effects in vivo.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Oncology
Hong-Gui Xu, Viktor Reshetnikov, Marit Wondrak, Lisa Eckhardt, Leoni A. Kunz-Schughart, Christina Janko, Rainer Tietze, Christoph Alexiou, Hannes Borchardt, Achim Aigner, Wenjie Gong, Michael Schmitt, Leopold Sellner, Steffen Daum, Huelya Gizem Oezkan, Andriy Mokhir
Summary: The study explores a novel N-alkylaminoferrocene-based prodrug that serves as a radiosensitizer by enhancing reactive oxygen species (ROS) levels specifically in cancer cells, affecting mitochondrial function, while sparing normal cells. By targeting mitochondria and inducing ROS simultaneously, the prodrug efficiently enhances the efficacy of radiotherapy and demonstrates a synergistic effect between radiotherapy and ROS amplification using NAAF-based compounds.
Article
Chemistry, Multidisciplinary
Joao P. M. Antonio, Joana Ines Carvalho, Ana S. Andre, Joana N. R. Dias, Sandra Aguiar, Helio Faustino, Ricardo M. R. M. Lopes, Luis F. Veiros, Goncalo J. L. Bernardes, Frederico A. Silva, Pedro M. P. Gois
Summary: ADCs are a new class of therapeutics combining cytotoxic drugs and antibodies to selectively deliver drugs to cancer cells. The synthesis of a ROS-responsive ADC in this study demonstrated the effectiveness of DABs and their potential for constructing different ROS-responsive linkers. DFT calculations showed a favorable energetic profile, enabling the site-selective functionalization of antibody domains and construction of homogeneous ADCs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Hulya Gizem Oezkan, Andriy Mokhir
Summary: Hybrid drugs containing ferrocene and phenol residues exhibit potent anticancer activity, but their mode of action, specificity, and metabolism need further investigation. In this study, we synthesized prodrugs of aminoferrocene-phenol hybrids and confirmed their activation in cancer cells while remaining inactive in normal cells. The anticancer activity of the prodrug relies on the generation of reactive oxygen species in cells.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Biophysics
Yuta Koda, Yukio Nagasaki
Summary: In this study, novel self-assembling antioxidants based on L-cysteine were developed to reduce the adverse effects of conventional antioxidants. These antioxidants showed high stability and low toxicity in vitro and in vivo.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Review
Chemistry, Inorganic & Nuclear
Joop A. Peters, Kristina Djanashvili
Summary: This review examines the chemical mechanisms of the interactions between boronic acids and N-acetylneuraminic acids, which have been widely used in biomedicine. It emphasizes that the affinity of boronic acids for N-acetylneuraminic acids is pH dependent and complementary to their affinity for other common monosaccharides. Various examples from the literature illustrate the unique pH profile of the boronic-N-acetylneuraminic acid interaction and its applications in biomedicine.
COORDINATION CHEMISTRY REVIEWS
(2023)
Review
Oncology
J. Delahousse, C. Skarbek, A. Paci
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Charles Skarbek, Silvia Serra, Hichem Maslah, Estelle Rascol, Raphael Labruere
BIOORGANIC CHEMISTRY
(2019)
Article
Oncology
Julia Delahousse, Charles Skarbek, Melanie Desbois, Jean-Luc Perfettini, Nathalie Chaput, Angelo Paci
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Editorial Material
Chemistry, Medicinal
Hichem Maslah, Stephanie Pethe, Raphael Labruere
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Hichem Maslah, Charles Skarbek, Catherine Gourson, Marie-Aude Plamont, Stephanie Pethe, Ludovic Jullien, Thomas Le Saux, Raphael Labruere
Summary: A new platform capable of generating cytotoxic agents through intramolecular cyclization has been reported, showing rapid and effective action against cancer cells. This innovative method offers potential for prodrug development in anticancer therapy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Environmental Sciences
Anais Espinosa, Sylvie Nelieu, Pascale Lieben, Charles Skarbek, Raphael Labruere, Pierre Benoit
Summary: This study focused on the photodegradation of methotrexate under two irradiation conditions, with experiments conducted at different pH levels to produce a variety of transformation products. The degradation kinetics were contrasted according to pH and irradiation wavelength, with identification of transformation products using UHPLC-MS/MS. The study found that the photoproducts formed at pH 7 were less toxic than the parent compound when assessed for cytotoxicity on A549 cancer cells.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Chemistry, Organic
Thi Hang Au, Charles Skarbek, Stephanie Pethe, Raphael Labruere, Jean-Pierre Baltaze, Thi Phuong Hoa Nguyen, Thi Thu Ha Vu, Giang Vo-Thanh
Summary: The Michael addition reaction was used to synthesize 27 derivatives of Tagitinin C, which showed similar biological activity to Tagitinin C against three human cancer cell lines and had enhanced water solubility for potential improvement in bioavailability and pharmacological profiles.
Editorial Material
Surgery
Jean Senemaud, Charles Skarbek
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
(2022)
Article
Environmental Sciences
Anais Espinosa, Estelle Rascol, Marta Abellan Flos, Charles Skarbek, Pascale Lieben, Eva Bannerman, Alba Diez Martinez, Stephanie Pethe, Pierre Benoit, Sylvie Nelieu, Raphael Labruere
Summary: The emission of pharmaceutical pollutants has caused contamination of aquatic ecosystems and drinking water. A method for designing environmentally-friendly drugs by introducing a water-responsive chemical group within the molecular structure has been reported. These new drugs can be easily and quickly fragmented, leading to lower cytotoxicity of the degradation products compared to the original drugs.
Letter
Surgery
Jean N. Senemaud, Charles Skarbek, Jonathan Vigne, Francois Rouzet, Yves Castier, Giuseppina Caligiuri
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
(2022)
Article
Neuroimaging
Charles Skarbek, Vania Anagnostakou, Emanuele Procopio, Mark Epshtein, Christopher M. Raskett, Romeo Romagnoli, Giorgio Iviglia, Marco Morra, Marta Antonucci, Antonino Nicoletti, Giuseppina Caligiuri, Matthew J. Gounis
Summary: The study suggests that coating clot retrieval devices with DNA-binding compounds can significantly improve the outcome of mechanical thrombectomy procedures in stroke patients.
JOURNAL OF NEUROINTERVENTIONAL SURGERY
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
