Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy; Department of Chemical Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy.
Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
Bioorg Chem. 2018 Dec;81:334-339. doi: 10.1016/j.bioorg.2018.08.023. Epub 2018 Aug 27.
HO-1 inhibition is considered a valuable anticancer approach. In fact, up-regulation of HO-1 had been repeatedly reported in many types of human malignancies, and in these clinical cases, poor outcomes are reported. To identify novel HO-1 inhibitors suitable for drug development, a scaffold-hopping strategy calculation was utilized to design novel derivatives. Different parts of the selected molecule were analyzed and the different series of novel compounds were virtually evaluated. The calculation for the linker moiety of the classical HO-1 inhibitors structure led us to compounds 5 and 6. A synthetic pathway for the two molecules was designed and the compounds were synthesized. The biological activity revealed an HO-1 inhibition of 0.9 and 54 μM for molecules 5 and 6 respectively. This study suggested that our scaffold-hopping approach was successful and these results are ongoing for further development.
血红素加氧酶-1（HO-1）抑制被认为是一种有价值的抗癌方法。事实上，HO-1 的上调已在许多类型的人类恶性肿瘤中被反复报道，而在这些临床病例中，报道的结果并不理想。为了寻找适合药物开发的新型 HO-1 抑制剂，我们利用基于骨架跃迁的策略计算来设计新型衍生物。对所选分子的不同部分进行分析，并对不同系列的新型化合物进行虚拟评估。对经典 HO-1 抑制剂结构的连接子部分的计算使我们得到了化合物 5 和 6。设计了这两种分子的合成途径，并合成了它们。生物活性显示化合物 5 和 6 的 HO-1 抑制率分别为 0.9 和 54μM。本研究表明，我们的基于骨架跃迁的方法是成功的，这些结果正在进一步开发中。
