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A series of -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity against primary patient-derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds was evaluated against glioma cell lines, with compound exhibiting promising glioma growth inhibitory properties. Compound was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. AKT signalling is one of the main oncogenic pathways in glioma and is often targeted for novel therapeutics. Indeed, AKT2 levels correlated with glioma malignancy and poorer patient survival. Compound inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells and exhibited potent EC against glioblastoma cell lines. Although exhibiting potency against glioma cells, exhibited significantly less cytotoxicity against non-cancerous cells even at fourfold-fivefold the concentration. Herein we establish a novel biochemical kinase inhibitory function for -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles and further report their anti-glioma activity for the first time.KEY MESSAGEAnti-glioma pyrano[2,3-c]pyrazole inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. also displayed PKBβ/AKT2 inhibitory activity. is nontoxic towards non-cancerous cells.

一系列 -(4-氯苯基)取代的吡喃并[2,3-c]吡唑被合成并筛选其抑制激酶的潜力，并对原代患者来源的胶质母细胞瘤 2D 细胞和 3D 神经球表现出抗癌活性。评价了 10 种化合物对神经胶质瘤细胞系的活性，其中化合物表现出有希望的神经胶质瘤生长抑制特性。化合物对 139 种纯化激酶进行了筛选，对激酶 AKT2/PKBβ 表现出低微摩尔活性。AKT 信号通路是神经胶质瘤的主要致癌途径之一，经常被用于新型治疗方法。事实上，AKT2 水平与神经胶质瘤的恶性程度和患者的生存预后相关。化合物抑制原代患者来源的神经胶质瘤干细胞中的 3D 神经球形成，并对神经母细胞瘤细胞系表现出强大的 EC。尽管对神经胶质瘤细胞表现出活性，但化合物对非癌细胞的细胞毒性明显较低，即使在四倍至五倍浓度下也是如此。本文建立了一种新型的 -(4-氯苯基)取代的吡喃并[2,3-c]吡唑的生化激酶抑制功能，并首次报道了其抗神经胶质瘤活性。