Abstract

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.

摘要

多形胶质母细胞瘤（GBM）是最致命，最常见的原发性恶性脑肿瘤。GBM患者的中位生存期约为一年，这是由于神经胶质瘤细胞弥漫性侵袭的性质所致，因此难以对肿瘤进行完整的手术切除。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相关的材料中的MMP抑制作用。使用伊洛马司他Leu-Trp主链，我们合成了新型磺酰胺，并监测了这些化合物在表达MMP3的条件培养基中的性能。根据本文讨论的结果，我们证明了基于磺酰胺的MMPI（包括AP-3，AP-6和AP-7）的性能。