In spite of progress in understanding biology of glioblastoma (GBM), this tumor remains incurable with a median survival rate of 15 months. Previous studies have shown that 2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FPDT) and 2-(3-chlorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (CPDT) diminished viability of cancer cell lines of different origin. In the current study, we have examined activity of these compounds in several GBM cell lines and patient-derived GBM cells. We have also designed, synthesized and evaluated anti-GBM activity of novel 1,3,4-thiadiazole derivatives containing additional Cl or CH2CH3 substitute at C5-position of 2,4-dihydroxyphenyl. The tested compounds presented a considerable cytotoxicity against all GBM cell lines examined as well as patient-derived GBM cells. They were 15-110 times more potent than temozolomide, the first-line chemotherapeutic agent for GBM. Notably, in anticancer concentrations three of the derivatives were not toxic to human astrocytes. FPDT appeared to be the most promising compound with IC50 values between 45 μM and 68 μM for GBM cells and >100 μM for astrocytes. It augmented activity of temozolomide and inhibited proliferation migration and invasion of GBM cells. Treatment with FPDT diminished phosphorylation level of GSK3β and AKT. Pretreatment with PDGF-BB, an AKT activator, partially protected cells from death caused by FPDT, indicating that FPDT-mediated decrease in cell viability is causatively related to the inhibition of the AKT pathway.Keywords:AKT pathway; Anti-glioblastoma compound; Glioblastoma; Proliferation; Thiadiazole derivative; Viability.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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