| RRC ID |
72195
|
| 著者 |
Ciftci HI, Radwan MO, Sever B, Hamdy AK, Emirdağ S, Ulusoy NG, Sozer E, Can M, Yayli N, Araki N, Tateishi H, Otsuka M, Fujita M, Altintop MD.
|
| タイトル |
EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas. In this context, a series of pentacyclic triterpene analogues were subjected to in vitro and in silico assays, which were conducted to assess their potency as EGFR-targeted anti-glioma agents. In particular, compound 10 was the most potent anti-glioma agent with an IC50 value of 5.82 µM towards U251 human glioblastoma cells. Taking into account its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), compound 10 exerts selective antitumor action towards Jurkat human leukemic T-cells. This compound also induced apoptosis and inhibited EGFR with an IC50 value of 9.43 µM compared to erlotinib (IC50 = 0.06 µM). Based on in vitro and in silico data, compound 10 stands out as a potential orally bioavailable EGFR-targeted anti-glioma agent endowed with the ability to cross the blood-brain barrier (BBB).
|
| 巻・号 |
22(20)
|
| 公開日 |
2021-10-11
|
| DOI |
10.3390/ijms222010945
|
| PII |
ijms222010945
|
| PMID |
34681605
|
| PMC |
PMC8537327
|
| MeSH |
Apoptosis / drug effects
Binding Sites
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Cell Line, Tumor
Cell Survival / drug effects
Drug Screening Assays, Antitumor
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / metabolism
Glioma / metabolism
Glioma / pathology
Half-Life
Humans
Leukocytes, Mononuclear / cytology
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / metabolism
Molecular Docking Simulation
Pentacyclic Triterpenes / chemistry*
Pentacyclic Triterpenes / metabolism
Pentacyclic Triterpenes / pharmacology
|
| IF |
4.556
|
| リソース情報 |
| ヒト・動物細胞 |
U251(RCB0461) |
