ADME/toxicity prediction and antitumor activity of novel nitrogenous heterocyclic compounds designed by computer targeting of alkylglycerone phosphate synthase

作者：Zhu, Yu^*; Han, Yuan; Ma, Ying; Yang, Ping

来源：Oncology Letters, 2018, 16(2): 1431-1438.

DOI：10.3892/ol.2018.8873

• computer-aided drug design
• alkylglycerone phosphate synthase
• nitrogenous heterocyclic compound

Alkylglycerone phosphate synthase (AGPS) is an oncogene and can be considered as an antitumor drug target. The aim of the present study was to design novel nitrogenous heterocyclic compound improving targetability by computer-aided drug design technology targeting AGPS. A total of 12 nitrogenous heterocyclic compounds were designed and predicted the absorption, distribution, metabolism and excretion parameters/toxicity. Their activity in terms of proliferation inhibition, cell cycle arrest and apoptosis induction was then measured using an MTS assay and a high-content screening system in U251 cells. The results showed that anti-glioma activity was present in compounds N4, N5, N6, N7, N8 and N12, which was in accordance with the computer prediction. Therefore, these compounds may be suitable for the development of a novel glioma therapeutic drug.

• 出版日期2018-8
• 单位天津医科大学; 天津市环湖医院