Synthesis and antitumor activity of novel steroidal imidazolium salt derivatives
| Autor: | Yaxiao Gong, Hongbin Zhang, Zhuo Chen, Liang Gong, Guogang Deng, Bei Zhou, Dongmei Wu, Xiao-Dong Yang, Jing Wang, Yan Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Benzimidazole
Stereochemistry Salt (chemistry) Antineoplastic Agents Apoptosis 01 natural sciences Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Cytotoxic T cell IC50 Cell Proliferation 030304 developmental biology Pharmacology chemistry.chemical_classification 0303 health sciences Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Cell growth Organic Chemistry Imidazoles Cell Cycle Checkpoints General Medicine 0104 chemical sciences chemistry Cell culture Salts Steroids Drug Screening Assays Antitumor G1 phase |
| Zdroj: | European Journal of Medicinal Chemistry. 168:232-252 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2019.02.025 |
| Popis: | Sixty-one novel steroidal imidazolium salt derivatives were synthesized and evaluated in vitro against a panel of human tumor cell lines. The results showed that diosgenin‒imidazolium salt derivatives displayed much higher cytotoxic activities than cholesterol‒imidazolium salts and dehydroepiandrosterone‒imidazolium salts. The SARs results suggested that the existence of substituted 5,6-dimethyl-benzimidazoles or benzimidazole ring and substitution of the imidazolyl-3α-position with a 2-bromobenzyl or 2-naphthylmethyl group could be critical for promoting cytotoxic activity. Diosgenin‒imidazolium salt a30 was found to be the most potent compound with IC50 values of 0.44–0.79 μM against five human tumor cell lines. Compound a24 showed inhibitory activity selectively against SMMC-7721 cell lines with IC50 value of 0.21 μM and 54-fold more sensitive to DDP. Moreover, compound a30 inhibited cell proliferation through inducing the G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect