| RRC ID |
69557
|
| 著者 |
Kohyama A, Kim MJ, Yokoyama R, Sun S, Omar AM, Phan ND, Meselhy MR, Tsuge K, Awale S, Matsuya Y.
|
| タイトル |
Structure-activity relationship and mechanistic study on guggulsterone derivatives; Discovery of new anti-pancreatic cancer candidate.
|
| ジャーナル |
Bioorg Med Chem
|
| Abstract |
Pancreatic cancer is one of the deadliest types of malignancies. A new intervention aiming to combat pancreatic cancer is targeting its extra-ordinary ability to tolerate nutrition starvation, a phenomenon known as "Austerity". As a part of a research program aiming to develop a new-generation of anticancer agents, known as "anti-austerity agents", guggulsterone derivatives (GSDs) were identified as unique anti-austerity agents in terms of potency and selectivity. These agents are able to exert preferential cytotoxic activity only under nutrient-deprived conditions with little or no toxicity under normal conditions. In the present study, a library of 14 GSDs was synthesized and screened against PANC-1 human pancreatic cells. Among tested compounds, GSD-11 showed the most potent activity with PC50 a value of 0.72 μM. It also inhibited pancreatic cancer cell migration and colony formation in a concentration-dependent manner. A mechanistic study revealed that this compound can inhibit the activation of the Akt/mTOR signaling pathway. Therefore, GSD-11 could be a promising lead compound for the anticancer drug discovery against pancreatic cancer.
|
| 巻・号 |
54
|
| ページ |
116563
|
| 公開日 |
2022-1-15
|
| DOI |
10.1016/j.bmc.2021.116563
|
| PII |
S0968-0896(21)00571-X
|
| PMID |
34942553
|
| MeSH |
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Discovery*
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Pancreatic Neoplasms / drug therapy*
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology
Pregnenediones / chemical synthesis
Pregnenediones / chemistry
Pregnenediones / pharmacology*
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / drug effects
Structure-Activity Relationship
TOR Serine-Threonine Kinases / antagonists & inhibitors
TOR Serine-Threonine Kinases / metabolism
Tumor Cells, Cultured
|
| IF |
3.073
|
| リソース情報 |
| ヒト・動物細胞 |
PANC-1(RCB2095) |
