New analogs of SYA013 as sigma-2 ligands with anticancer activity
| Autor: | Gladys Asong, Terrick Andey, Felix Amissah, Barbara A. Bricker, Xue Y. Zhu, Seth Y. Ablordeppey, Nazarius S. Lamango |
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| Rok vydání: | 2019 |
| Předmět: |
Cell Survival
Clinical Biochemistry Pharmaceutical Science Sigma-2 receptor Antineoplastic Agents Ligands 01 natural sciences Biochemistry Article Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Receptors sigma Receptor Molecular Biology 010405 organic chemistry Ligand Organic Chemistry Azepines Oxime 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Cell culture Cancer cell Toxicity Haloperidol Molecular Medicine Cisplatin Drug Screening Assays Antitumor Selectivity |
| Zdroj: | Bioorg Med Chem |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2019.04.012 |
| Popis: | Our previous study has revealed 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one·2HCl (SYA013) 1 as a sigma ligand with moderate selectivity for the sigma-2 receptor. Given the overexpression of sigma receptors in solid tumors and reports of sigma ligands with anticancer activities, we selected 1 for evaluation in several solid tumor cell lines. In addition, we have synthesized new analogs of 1 and now report that several of them bind preferentially at the sigma-2 receptor and have shown inhibition of several cancer cell lines including MDA-MB-231, MDA-MB-486, A549, PC-3, MIA PaCa-2 and Panc-1 cells. In particular, compounds 1 and 12 have demonstrated sub-micromolar activity against the Panc-1 cell line. It has also been observed that several of these compounds demonstrate selective toxicity toward cancer cells, when compared to normal cells. |
| Databáze: | OpenAIRE |
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