Novel naftopidil-related derivatives and their biological effects as alpha1-adrenoceptors antagonists and antiproliferative agents
| Autor: | Huang Yajian, Fei He, Min-Yi Huang, Ya Yang, Xia-Wen Liu, Liu Zhu, Junjun Huang, Mu Yuan, Yan Xiong, Xingjie Xu |
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| Rok vydání: | 2015 |
| Předmět: |
Antineoplastic Agents
Apoptosis Naphthalenes Pharmacology Piperazines Structure-Activity Relationship Cell Line Tumor Receptors Adrenergic alpha-1 Drug Discovery LNCaP medicine Animals Humans Structure–activity relationship IC50 Cell Proliferation Dose-Response Relationship Drug Molecular Structure Naftopidil Cell growth Chemistry Cell Cycle Organic Chemistry Antagonist General Medicine Cell culture Adrenergic alpha-1 Receptor Antagonists Rabbits Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 96:83-91 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2015.04.005 |
| Popis: | Eleven novel naftopidil-related compounds that contain amide and indole groups were designed and synthesized. The biological effects of these compounds on three α1-adrenoceptor subtypes and cancerous human prostate cell lines (PC-3, DU-145, and LNCaP) were determined. Compounds 2, 3, 5, 11, and 12 exhibited an α1-adrenoceptor antagonistic activity, whereas compounds 9, 10, and 12 displayed moderate antiproliferative activities. Compound 3 exhibited a significant α(1D/1A) blocking activity in isolated rat tissues (97.7- and 64.6-fold selective for α(1D) and α(1A) compared with α(1B)) but not a relevant cytotoxic activity. Compound 12 demonstrated a potent and selective α(1D/1A) antagonistic activity (47.9- and 19.1-fold for α(1D) and α(1A) compared with α1B) and a potent antiproliferative activity in PC-3 cells (IC50 = 15.70 μM). Further testing confirmed that compound 12 inhibited the growth of PC-3 cells by inducing apoptosis and G0/G1 cell cycle arrest, which was mediated by α1-adrenoceptor. Therefore, compound 12 is a potential multipotent agent that can act as an effective α1-adrenoceptor subtype antagonist for treating benign prostatic hyperplasia and a preventive medication against human prostate cancer. |
| Databáze: | OpenAIRE |
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