Synthesis and Characterization of a Series of Temozolomide Esters and Its Anti-glioma Study
Autor: | Liangxiao Wang, Chunjie Sha, Yawen Yu, Liuxiang Chu, Kaoxiang Sun, Aiping Wang, Ronglin Kan, Junping Han, Xinran Xi |
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Rok vydání: | 2021 |
Předmět: |
Drug
media_common.quotation_subject Pharmaceutical Science 02 engineering and technology Drug resistance Pharmacology 030226 pharmacology & pharmacy Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Glioma Temozolomide medicine Animals Cytotoxicity IC50 media_common Brain Neoplasms Chemistry Esters Prodrug 021001 nanoscience & nanotechnology medicine.disease Xenograft Model Antitumor Assays Rats Drug Resistance Neoplasm Lipophilicity Glioblastoma 0210 nano-technology medicine.drug |
Zdroj: | Journal of Pharmaceutical Sciences. 110:3431-3438 |
ISSN: | 0022-3549 |
Popis: | Temozolomide is a first-line therapeutic drug for glioblastoma (GBM), and it has a low solubility, short biological half-life, and resistance to drug limits in clinical applications. Therefore, it is necessary to find more effective anti-tumor drugs to overcome drug resistance and enhance its anti-glioma activity. We therefore used n-butanol, n-hexanol, n-octanol, 1-dodecanol and 1-hexadecanol to synthesize a series of temozolomide ester compounds (TMZEs) and then investigated their physicochemical properties and anti-glioma efficacy. Our results showed that TMZEs had a higher lipophilicity compared to TMZ and could stably exist in plasma and brain homogenates. TMZEs had significantly increased cytotoxicity and cellular uptake in C6 glioma cells as chain lengths increased. Additionally, the IC50 of TMZ-16E towards TMZ-resistant cells (T98G) was 85.9-fold lower than that of TMZ (p |
Databáze: | OpenAIRE |
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