新型恶二唑衍生物的合成及其对多种癌细胞系的细胞毒性活性。

Synthesis of novel oxadiazole derivatives and their cytotoxic activity against various cancer cell lines.

作者信息

Sucu Bilgesu Onur, Koç Elif Beyza

机构信息

Research Institute for Health Sciences and Technologies (SABITA), Center of Drug Discovery and Development, İstanbul Medipol University, İstanbul, Turkey.

Department of Medical Services and Techniques, Vocational School of Health Services, İstanbul Medipol University, İstanbul, Turkey.

出版信息

Turk J Chem. 2022 Mar 12;46(4):1089-1096. doi: 10.55730/1300-0527.3417. eCollection 2022.

Caffeic acid (CA), ferulic acid (FA) and caffeic acid phenethyl ester (CAPE) have a broad anticancer effect on various cell lines. In this study, nine ferulic and caffeic acid-based 1,2,4 and 1,3,4 oxadiazole molecular hybrids were synthesized and their cytotoxic activity was evaluated mainly against Glioblastoma (GBM) cell lines. Compounds 1 and 5 exhibited the highest inhibitory activity against three different GBM cell lines (LN229, T98G, and U87), without toxicity to healthy human mesenchymal stem cells (hMSC). In addition, their cytotoxicity was also evaluated against three additional cancer cell lines and more inhibitory results were found than GBM cell lines. The IC values of compound 5 in U87, T98G, LN229, SKOV3, MCF7, and A549 cells were determined as 35.1, 34.4, 37.9, 14.2, 30.9, and 18.3 μM. In the light of biological activity studies, the developed compounds have a high potential to lead studies for the development of new drug candidates for the treatment of cancer.

咖啡酸（CA）、阿魏酸（FA）和咖啡酸苯乙酯（CAPE）对多种细胞系具有广泛的抗癌作用。在本研究中，合成了九种基于阿魏酸和咖啡酸的1,2,4和1,3,4-恶二唑分子杂化物，并主要针对胶质母细胞瘤（GBM）细胞系评估了它们的细胞毒性活性。化合物1和5对三种不同的GBM细胞系（LN229、T98G和U87）表现出最高的抑制活性，且对健康人骨髓间充质干细胞（hMSC）无毒性。此外，还针对另外三种癌细胞系评估了它们的细胞毒性，发现其抑制结果比GBM细胞系更多。化合物5在U87、T98G、LN229、SKOV3、MCF7和A549细胞中的IC值分别测定为35.1、34.4、37.9、14.2、30.9和18.3 μM。根据生物活性研究，所开发的化合物具有很高的潜力，可引领开发用于治疗癌症的新药候选物的研究。