新型 1,2,3,4-四氢异喹啉衍生物的合成及体外评价作为有效的抗神经胶质瘤药物。

Synthesis and in vitro evaluation of novel 1,2,3,4-tetrahydroisoquinoline derivatives as potent antiglioma agents.

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, Egypt.

出版信息

Anticancer Agents Med Chem. 2014 Mar;14(3):473-82. doi: 10.2174/18715206113139990328.

DOI:10.2174/18715206113139990328

Abstract

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.

摘要

多形性胶质母细胞瘤（GBM）仍然需要改进的化疗解决方案。为了发现用于 GBM 的新型化疗药物，我们将新型四氢异喹啉（THI）类似物鉴定为抗神经胶质瘤药物。本研究报告了在四种已建立的人神经胶质瘤细胞系（T98、U87、LN18 和 A172）中新型 THI 衍生物的设计、合成和体外评价。我们的构效关系（SAR）研究表明，联苯和 THI 环之间碳连接的重要修饰产生了 EDL-360（12），作为一种有效的抗神经胶质瘤药物（LN18；IC50：5.42±0.06 μM），并被认为是我们用于进一步临床前研究的新的候选药物。