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Repurposing sodium stibogluconate as an uracil DNA glycosylase inhibitor against prostate cancer using a time-resolved oligonucleotide-based drug screening platform.
Nao, Sang-Cuo; Huang, Le-Sheng; Shiu-Hin Chan, Daniel; Wang, Xueliang; Li, Guo-Dong; Wu, Jia; Wong, Chun-Yuen; Wang, Wanhe; Leung, Chung-Hang.
Afiliación
  • Nao SC; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
  • Huang LS; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
  • Shiu-Hin Chan D; Department of Chemistry, City University of Hong Kong, Hong Kong, China.
  • Wang X; Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, 45 South Gaoxin Road, Shenzhen 518057, China.
  • Li GD; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
  • Wu J; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
  • Wong CY; Department of Chemistry, City University of Hong Kong, Hong Kong, China. Electronic address: acywong@cityu.edu.hk.
  • Wang W; Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, 45 South Gaoxin Road, Shenzhen 518057, China. Electronic address: whwang0206@nwpu.edu.cn.
  • Leung CH; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China; Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau, China; Macao Centre for Research and Development in
Bioorg Chem ; 144: 107176, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38330721
ABSTRACT
Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Uracil-ADN Glicosidasa Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans / Male Idioma: En Revista: Bioorg Chem Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Uracil-ADN Glicosidasa Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans / Male Idioma: En Revista: Bioorg Chem Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos