Singh Ashok K, Raj Vinit, Rai Amit, Keshari Amit K, Saha Sudipta
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Rae Bareli Road, Lucknow 226025, India.
Future Sci OA. 2017 Jan 4;3(1):FSO168. doi: 10.4155/fsoa-2016-0079. eCollection 2017 Mar.
A new series of compounds () bearing indole-fused benzooxazepine was synthesized, characterized and evaluated for anticancer activity.
MATERIALS & METHODS: In this study, all the synthesized compounds were screened via anticancer testing on Hep-G2 cancer cell line. A computational study was carried out on cancer-related targets including IL-2, IL-6, COX-2 Caspase-3 and Caspase-8.
Some of the synthesized compounds effectively controlled the growth of cancerous cells.
The most active compounds - , , , and - exemplify notable anticancer profile with GI <10 μg/ml. Preliminary structure-activity relationship among the tested compounds can produce an assumption that the electronegative groups at phenyl ring attached with indole-fused benzooxazepine are instrumental for the activity. Molecular docking study showed crucial hydrogen bond and π-π stacking interactions, with good ADMET profiling and molecular dynamic simulation.
合成了一系列含吲哚并苯并恶唑嗪的新化合物，对其进行了表征并评估了抗癌活性。
在本研究中，所有合成化合物均通过对Hep-G2癌细胞系进行抗癌测试来筛选。对包括白细胞介素-2、白细胞介素-6、环氧化酶-2、半胱天冬酶-3和半胱天冬酶-8在内的癌症相关靶点进行了计算研究。
一些合成化合物有效地控制了癌细胞的生长。
活性最高的化合物—— 、 、 、 和 ——表现出显著的抗癌活性，胃肠道半数抑制浓度（GI）<10μg/ml。受试化合物之间初步的构效关系可以得出一个假设，即与吲哚并苯并恶唑嗪相连的苯环上的电负性基团对活性起作用。分子对接研究显示了关键的氢键和π-π堆积相互作用，具有良好的药物代谢动力学性质和分子动力学模拟。
