論文 - 詳細
| RRC ID | 69674 |
|---|---|
| 著者 | Roayapalley PK, Dimmock JR, Contreras L, Balderrama KS, Aguilera RJ, Sakagami H, Amano S, Sharma RK, Das U. |
| タイトル | Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts. |
| ジャーナル | Molecules |
| Abstract |
A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a-h and related quaternary ammonium salts 4a-h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series 3 and 4 to be potent cytotoxins with submicromolar CC50 values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure-activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, 3a-h are cytotoxic towards a number of leukemic and colon cancer cells. 4b,c lowered the mitochondrial membrane potential in CEM cells, and 4d induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely 3c,d and 4c-e, were identified as lead molecules that have drug-like properties. |
| 巻・号 | 26(23) |
| 公開日 | 2021-11-25 |
| DOI | 10.3390/molecules26237132 |
| PII | molecules26237132 |
| PMID | 34885719 |
| PMC | PMC8659243 |
| MeSH | Antineoplastic Agents / chemical synthesis* Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology Apoptosis / drug effects Cell Line, Tumor Cell Proliferation / drug effects Colonic Neoplasms / drug therapy* Humans Oximes / chemical synthesis* Oximes / chemistry Oximes / pharmacology Quantitative Structure-Activity Relationship Quaternary Ammonium Compounds / chemical synthesis* Quaternary Ammonium Compounds / chemistry Quaternary Ammonium Compounds / pharmacology |
| IF | 3.267 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Ca9-22(RCB1976) HSC-2(RCB1945) HSC-4(RCB1902) |