Synthesis and in vitro evaluation of novel 1,2,3,4-tetrahydroisoquinoline derivatives as potent antiglioma agents
| Autor: | Duane D. Miller, Renukadevi Patil, Ryan Yates, Eldon E. Geisert, Asres Likeselam, XiangDi Wang, Amira Hosni-Ahmed, Shivaputra A. Patil, Terreia S. Jones |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pharmacology
Cancer Research Chemistry Tetrahydroisoquinoline Brain Neoplasms Cell Survival Tetrahydroisoquinoline derivatives Antineoplastic Agents Glioma In vitro nervous system diseases chemistry.chemical_compound Structure-Activity Relationship Cell culture Cell Line Tumor Tetrahydroisoquinolines Molecular Medicine Structure–activity relationship Humans U87 Drug Screening Assays Antitumor IC50 Linker |
| Zdroj: | Anti-cancer agents in medicinal chemistry. 14(3) |
| ISSN: | 1875-5992 |
| Popis: | Glioblastoma Multiforme (GBM) continues to demand improved chemotherapeutic solutions. In order to discover novel chemotherapeutic agents for GBM, we identified novel tetrahydroisoquinoline (THI) analogs as antiglioma agents. The present study reports the design, synthesis and in vitro evaluation of new THI derivatives in four established human glioma cell lines (T98, U87, LN18 and A172). Our structure activity relationship (SAR) studies revealed that the important modification of the carbon linker between the biphenyl and THI ring yielded EDL-360 (12) as a potent antiglioma agent (LN18; IC50: 5.42 ± 0.06 μM) and is considered to be our new lead drug candidate for further preclinical studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|