Design, Synthesis, and Hypoxia-Inducible Factor-1α Inhibitory Activity Evaluation of Panaxadiol Derivatives Containing a Thiazole Moiety.

The hypoxia-inducible factor-1α (HIF-1α) pathway has been implicated in tumor angiogenesis, growth, and metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for cancer. Thiazole derivatives have been reported to have diverse biological activities, especially in terms of anti-tumor. Consequently, we hypothesized that the introduction of a thiazole functional group in PD was likely to improve the biological potency. Here, three series of PD derivatives containing a thiazole moiety were synthesized, including (a) sulfonyl-containing thiazole derivatives (5 a-l), (b) urea-containing thiazole derivatives (7 a-i), and (c) thiourea-containing thiazole derivatives (9 a-i), and evaluated for HIF-1α inhibitory activity using a Hep3B cell-based luciferase reporter assay. The results showed that about 1/3 of the target compounds showed moderate or strong HIF-1α inhibitory activity, among which compounds 5 d and 7 b showed the strongest inhibitory activity with IC50 values of 17.37 and 6.42 µM, respectively, and did not show any significant cytotoxicity. Western blot assay results indicated that these two compounds exhibited more potent inhibition, compared with panaxadiol, of the expression of HIF-1α protein in Hep3B cells at a concentration of 50 µM. Molecular docking experiments were also performed to investigate the structure-activity relationship. Compounds 5 d and 7 b can be used as leads for further study and development of novel antitumor drugs.

GNG5 is an unfavourable independent prognostic indicator of gliomas.

Gliomas are the most common primary brain tumours, and glioblastomas (GBMs) are subgrouped into four distinct molecular subtypes. This study aimed to identify the potential gene related to glioma progression. Weighted gene co-expression network analysis (WGCNA) was used to explore the related gene. Correlation, ROC, survival and Cox regression analyses were performed. Blue module was strongly associated with WHO grade (r = .65, P = 1e-19). GNG5 in gliomas was overexpressed compared with normal samples and associated with clinicopathologic characteristics. GNG5 was frequent in Mesenchymal subtype and lowly expressed in Proneural subtype of GBMs. Survival and Cox regression analyses showed that glioma patients with GNG5 overexpression had shorter survival time, and GNG5 was an independent prognostic indicator of overall survival. Overall, GNG5 expression is closely associated with clinicopathologic characteristics and is an independent prognostic indicator for glioma patients, as well as a promising subtype-associated biomarker in molecular classification of gliomas.