使用侵袭性神经胶质瘤细胞的条件培养基检测基质金属蛋白酶 3 的磺胺类抑制剂。

Department of Chemistry, Brandon University, Brandon, Canada.

Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, Vancouver, Canada.

J Enzyme Inhib Med Chem. 2020 Dec;35(1):672-681. doi: 10.1080/14756366.2020.1715387.

Glioblastoma multiforme (GBM) is the deadliest and the most common primary malignant brain tumour. The median survival for patients with GBM is around one year due to the nature of glioma cells to diffusely invade that make the complete surgical resection of tumours difficult. Based upon the connexin43 (Cx43) model of glioma migration we have developed a computational framework to evaluate MMP inhibition in materials relevant to GBM. Using the ilomastat Leu-Trp backbone, we have synthesised novel sulphonamides and monitored the performance of these compounds in conditioned media expressing MMP3. From the results discussed herein we demonstrate the performance of sulfonamide based MMPIs included AP-3, AP-6, and AP-7.

多形性胶质母细胞瘤（GBM）是最致命和最常见的原发性恶性脑肿瘤。由于神经胶质瘤细胞弥漫性浸润，使肿瘤完全手术切除变得困难，因此 GBM 患者的中位生存期约为一年。基于神经胶质瘤迁移的连接蛋白 43（Cx43）模型，我们开发了一个计算框架来评估与 GBM 相关材料中基质金属蛋白酶（MMP）抑制的效果。使用依洛美萨（ilomastat）Leu-Trp 骨架，我们合成了新的磺酰胺类化合物，并监测了这些化合物在表达 MMP3 的条件培养基中的性能。从本文讨论的结果中，我们证明了基于磺酰胺的 MMPIs（AP-3、AP-6 和 AP-7）的性能。