The discovery of novel sanjuanolide derivatives as chemotherapeutic agents targeting castration-resistant prostate cancer
| Autor: | Zhiguo Liu, Yue Ma, Xiangjuan Chen, Guangbao Wang, Sheng Shu, Qianwen Zhang, Yunbei Xiao, Nan Wang, Xiaojing Chen, Ali Mohammed Mohammed Alsayed, Peng Liu, Lu liu, Xiaohui Zheng |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Programmed cell death DNA damage Cell Survival Antineoplastic Agents Castration resistant urologic and male genital diseases 01 natural sciences Biochemistry Prostate cancer Structure-Activity Relationship Chalcones Drug Discovery medicine Tumor Cells Cultured Humans In patient Molecular Biology IC50 Cause of death Cell Proliferation Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry medicine.disease 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Prostatic Neoplasms Castration-Resistant Apoptosis Cancer research Drug Screening Assays Antitumor |
| Zdroj: | Bioorganic chemistry. 111 |
| ISSN: | 1090-2120 |
| Popis: | There remains a critical need for more effective therapies for the treatment of castration-resistant prostate cancer (CRPC), which is the leading cause of death in patients with prostate cancer. In this study, a series of sanjuanolide derivatives were designed, synthesized and evaluated as potential anti-CRPC agents. Most of the compounds had excellent selectivity for CRPC cells with IC50 values 100 µM. The representative compound S07 slowed down the proliferative rate of CRPC cells, promoted cell apoptosis and caused G2/M phase accumulation, as well as G1/G0 phase reduction. Further mechanistic studies showed that S07 treatment triggered intense DNA damage and provoked strong DNA damage response in a dose-dependent manner. These findings suggested that sanjuanolide derivatives, especially S07, selectively induced CRPC cell death by triggering intense DNA damage and DNA damage response. |
| Databáze: | OpenAIRE |
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