a Department of Pharmaceutical Chemistry , SPP School of Pharmacy and Technology Management, SVKM's NMIMS , Mumbai , India.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):972-977. doi: 10.1080/14756366.2018.1474211.
Human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2), being an age-old target, has attracted attention recently for anticancer drug development. Mycophenolic acid (MPA), a well-known immunosuppressant drug, was used a lead structure to design and develop modestly potent and selective analogues. The steep structure-activity relationship (SAR) requirements of the lead molecule left little scope to synthesise newer analogues. Here, newer MPA amides were designed, synthesised and evaluated for hIMPDH2 inhibition and cellular efficacy in breast, prostate and glioblastoma cell lines. Few title compounds exhibited cellular activity profile better than MPA itself. The observed differences in the overall biological profile could be attributed to improved structural and physicochemical properties of the analogues over MPA. This is the first report of the activity of MPA derivatives in glioblastoma, the most aggressive brain cancer.
人肌苷 5'-单磷酸脱氢酶 2（hIMPDH2）作为一个古老的靶点，最近引起了人们对抗癌药物开发的关注。霉酚酸（MPA）是一种著名的免疫抑制剂药物，被用作设计和开发适度有效和选择性类似物的先导结构。该先导分子陡峭的结构-活性关系（SAR）要求几乎没有余地来合成更新的类似物。在这里，设计、合成了新型 MPA 酰胺，并评估了它们对乳腺癌、前列腺癌和神经胶质瘤细胞系中 hIMPDH2 的抑制作用和细胞功效。一些标题化合物的细胞活性谱优于 MPA 本身。观察到的整体生物学特征的差异可以归因于类似物相对于 MPA 改善了结构和物理化学性质。这是 MPA 衍生物在最具侵袭性的脑癌神经胶质瘤中活性的首次报道。
