Article
Food Science & Technology
Karolina Kowalska, Marta Justyna Koziel, Kinga Anna Urbanek, Dominika Ewa Habrowska-Gorczynska, Kamila Dominska, Agnieszka Wanda Piastowska-Ciesielska
Summary: This study indicates that AOH may affect basic processes in normal prostate epithelial cells, potentially leading to benign and malignant changes in prostate tissue.
Article
Biochemistry & Molecular Biology
Hao Yang, Fang-Ting Wang, Min Wu, Wenjie Wang, Keli Agama, Yves Pommier, Lin -Kun An
Summary: In this study, 11-aminoalkoxy substituted benzophenanthridine derivatives were synthesized as selective TDP1 inhibitors. Six compounds showed high TDP1 inhibition potency, and the most potent inhibitor 14 induced cellular TDP1cc formation and exhibited synergistic effect with topotecan in various cancer cell lines.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hao Yang, Xiao-Qing Zhu, Wenjie Wang, Yu Chen, Zhu Hu, Yu Zhang, De-Xuan Hu, Le-Mao Yu, Keli Agama, Yves Pommier, Lin-Kun An
Summary: This study explored the structure-activity relationship of furoquinolinedione and isoxazoloquinolinedione derivatives as TDP2 inhibitors, revealing that isoxazoloquinolinedione derivatives selectively showed high TDP2 inhibitory activity. The most potent compound, 3-(3,4-dimethoxyphenyl)isoxazolo[4,5-g]quinoline-4,9-dione, demonstrated TDP2 inhibitory activity with an IC50 value of 0.46 +/- 0.15μM, indicating potential for the development of selective TDP2 inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Yu Zhang, Hao Yang, Fang-Ting Wang, Xing Peng, Hai-Yang Liu, Qing-Jiang Li, Lin-Kun An
Summary: Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered DNA repair enzyme that can specifically repair topoisomerase 2 (TOP2)-mediated DNA damage. In this study, the natural product myrtucommulone E was identified as a selective TDP2 inhibitor and its synthesis was achieved through a key chemical reaction. Analogue (+)-29 showed good TDP2 inhibition potency and enhanced the cytotoxicity of TOP2 inhibitor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hao Yang, Chao Qin, Min Wu, Fang-Ting Wang, Wenjie Wang, Keli Agama, Yves Pommier, De-Xuan Hu, Lin-Kun An
Summary: A series of benzophenanthridinone derivatives with 11- or 12-substituted groups were designed and synthesized as potential inhibitors of topoisomerase IB (TOP1) and tyrosyl-DNA phosphodiesterase 1 (TDP1). The compounds 12 and 38 exhibited high TOP1 inhibitory activity (+++), while compounds 35, 37, 39, and 43 showed good TDP1 inhibition with IC50 values ranging from 10 to 18 μM. Compound 38 showed the highest cytotoxicity against HCT-116 cells (0.25 μM) by inducing cellular TOP1cc formation. The most potent TDP1 inhibitor 43 (10 μM) induced cellular TDP1cc formation, enhanced topotecan-induced DNA damage, and exhibited strong synergistic cytotoxicity with topotecan in both MCF-7 and MCF-7/TDP1 cells.
Article
Cell Biology
Natalia A. Lebedeva, Nadejda I. Rechkunova, Anton V. Endutkin, Olga I. Lavrik
Summary: This study investigates the interactions between key enzymes such as OGG1, APE1, and TDP1 involved in base excision repair (BER), as well as the regulatory proteins PARP1 and PARP2. The results demonstrate that these proteins form complexes with DNA intermediates, which can impact the DNA repair process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Genetics & Heredity
Alexandra L. Zakharenko, Nadezhda S. Dyrkheeva, Olga A. Luzina, Aleksandr S. Filimonov, Evgenii S. Mozhaitsev, Anastasia A. Malakhova, Sergey P. Medvedev, Suren M. Zakian, Nariman F. Salakhutdinov, Olga I. Lavrik
Summary: This study discovered a class of compounds derived from (-)-usnic acid that are capable of inhibiting both Tdp1 and Tdp2 DNA repair enzymes. These compounds protect wild-type cells from the cytotoxic effect of etoposide, but potentiate its action in Tdp2 knockout cells. The study suggests that the sensitizing effect of the compounds in the absence of Tdp2 may be due to their inhibition of Tdp1, which could take over the functions of Tdp2.
Article
Chemistry, Multidisciplinary
Xue Zhi Zhao, Wenjie Wang, George T. T. Lountos, Joseph E. E. Tropea, Danielle Needle, Yves Pommier, Terrence R. R. Burke Jr
Summary: Researchers have designed and synthesized phosphonic acid-containing variants of TDP1 inhibitors, which can mimic the structure of the substrate when bound to TDP1. By analyzing the crystal structures of TDP1 complexed with these inhibitors, the study reveals that phosphonic acid functionality may better replicate the substrate binding interactions of TOP1-DNA than carboxylic acid functionality.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nadezhda S. Dyrkheeva, Aleksandr S. Filimonov, Olga A. Luzina, Alexandra L. Zakharenko, Ekaterina S. Ilina, Anastasia A. Malakhova, Sergey P. Medvedev, Johannes Reynisson, Konstantin P. Volcho, Suren M. Zakian, Nariman F. Salakhutdinov, Olga Lavrik
Summary: Usnic acid derivatives show potential in cancer treatment as inhibitors that bind to topoisomerase 1, with low cytotoxicity. In experiments, some compounds had effects on the cytotoxicity of the anticancer drug topotecan in both cancerous and non-cancerous cells.
Article
Chemistry, Medicinal
Kseniya Kovaleva, Olga Yarovaya, Konstantin Ponomarev, Sergey Cheresiz, Amirhossein Azimirad, Irina Chernyshova, Alexandra Zakharenko, Vasily Konev, Tatiana Khlebnikova, Evgenii Mozhaytsev, Evgenii Suslov, Dmitry Nilov, Vytas Svedas, Andrey Pokrovsky, Olga Lavrik, Nariman Salakhutdinov
Summary: In this study, a series of novel abietyl and dehydroabietyl ureas, thioureas, amides, and thioamides bearing adamantane moieties were designed, synthesized, and evaluated for their inhibitory activities against tyrosil-DNA-phosphodiesterase 1 (TDP1). The synthesized compounds showed promising inhibitory activities against TDP1 and low cytotoxicity in T98G glioma cell line. Molecular docking analysis suggested that adamantane derivatives of resin acids bind to TDP1 covalent intermediate, forming interactions with specific residues and the substrate fragment.
Article
Environmental Sciences
Eszter Fliszar-Nyul, Illes Bock, Rita Csepregi, Lajos Szente, Istvan Szabo, Zsolt Csenki, Miklos Poor
Summary: This study found that Sugammadex forms a stable complex with AOH, effectively eliminating AOH-induced toxicity in HeLa cells. Different CDs also have a certain reduction effect on AOH toxicity in zebrafish embryos, with native beta-CD showing the strongest protective effect.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2022)
Article
Engineering, Environmental
Hongrui Guo, Yujuan Ouyang, Jiaqi Wang, Hengmin Cui, Huidan Deng, Xinyue Zhong, Zhijie Jian, Huan Liu, Jing Fang, Zhicai Zuo, Xun Wang, Ling Zhao, Yi Geng, Ping Ouyang, Huaqiao Tang
Summary: Copper is essential but over-exposure can lead to adverse health effects. CuSO4 was found to induce spermatogenesis disorder through oxidative stress-mediated DNA damage and apoptosis, impairing male reproductive function.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Ireneusz Litwin, Seweryn Mucha, Ewa Pilarczyk, Robert Wysocki, Ewa Maciaszczyk-Dziubinska
Summary: In this study, it was found that trivalent antimony can cause various forms of DNA damage, including replication and oxidative DNA damage, and affect the activation of DNA damage checkpoints and formation of recombination repair centers in the model organism Saccharomyces cerevisiae.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Wei Zhao, Zhongjie Liu, Jiaming Luo, Changqing Ma, Luying Lai, Zhengyuan Xia, Shiyuan Xu
Summary: The study indicates that PARP-1 plays a key role in repairing oxidative DNA damage induced by bupivacaine, with interactions with XPD protein contributing to DNA integrity maintenance.
Article
Chemistry, Medicinal
Xia Wei, Fang-Ting Wang, Mei-Xia Si-Tu, Hao Fan, Jin-Shan Hu, Hao Yang, Shan-Yue Guan, Lin-Kun An, Cui-Xian Zhang
Summary: Four new benzodipyran racemates, representing a rare pyrano[4,3-h]chromene scaffold, were isolated from a soft-coral-derived fungus. The structures and configurations of all the compounds were determined using various analytical methods. The compounds' TDP1 inhibition activity and photophysical properties were evaluated.