Design, synthesis and biological evaluation of new steroidal β-triazoly enones as potent antiproliferative agents
| Autor: | Ya-Zhen You, Li-Hua Huang, Jia-Wen Guo, Hong-Min Liu, Zeng-Hui Wu, Ming-Jie Huang, Zhao Jianwei |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_treatment
Clinical Biochemistry 030209 endocrinology & metabolism Antineoplastic Agents Biochemistry Steroid 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Endocrinology Cell Movement Cell Line Tumor medicine Potency Humans Neoplasm Invasiveness Molecular Biology IC50 Cell Proliferation Pharmacology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Cell migration Ketones Triazoles Condensation reaction 030220 oncology & carcinogenesis Drug Design Cancer cell Antiproliferative Agents Click chemistry Steroids Drug Screening Assays Antitumor |
| Zdroj: | Steroids. 150 |
| ISSN: | 1878-5867 |
| Popis: | β-Triazoly enones are biologically interesting scaffolds, incorporation of such scaffolds into the steroid nucleus may generate new bioactive steroids and further enrich structural types of steroids. In this work, a series of new steroidal β-triazoly enones were synthesized based on click chemistry and Claisen–Schmidt condensation reaction and further evaluated for their antiproliferative activity against a panel of cancer cells. Most of these compounds showed better potency against PC-3 and MGC-803 cells. Particularly, compound 5a inhibited PC-3 and MGC-803 cells potently with the IC50 values of 1.61 and 1.16 μM, respectively, and was less toxic toward GES-1 with an IC50 value of 20.72 μM. Further mechanistic studies showed that compound 5a inhibited migration and invasion of MGC-803 and PC-3 dose-dependently. Treatment with compound 5a varied mRNA levels and protein expression of EMT markers in both cells. Collectively, the steroidal β-triazoly enones could be potentially utilized to develop new anticancer agents with the ability of inhibiting cell migration and invasion. |
| Databáze: | OpenAIRE |
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