Synthesis, Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors.,ChemMedChem

当前位置： X-MOL 学术 › ChemMedChem › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Synthesis, Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors.
ChemMedChem ( IF 3.6 ) Pub Date : 2020-08-03 , DOI: 10.1002/cmdc.202000500
Lilia Clima ₁ , Bogdan Florin Craciun ₁ , Andrea Angeli _{1,

2} , Andrea Petreni _{1,

2} , Alessandro Bonardi ₃ , Alessio Nocentini ₃ , Fabrizio Carta ₂ , Paola Gratteri ₃ , Mariana Pinteala ₁ , Claudiu T Supuran ₂

Affiliation

We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low‐nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor‐associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor‐associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor‐bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.

中文翻译：

作为碳酸酐酶抑制剂的角鲨烯衍生物的合成、计算研究和体外活性评估。

我们报告了结合无毒角鲨烯支架和不同碳酸酐酶抑制剂 (CAI) 的新型分子。在低纳摩尔范围内，检测到磺胺衍生物对同种型 hCA II 的有效抑制作用，事实证明，与肿瘤相关的 hCA IX 和 XII 同种型相比，该亚型对这种同种型具有选择性。另一方面，香豆素衍生物对肿瘤相关的同工型 CA IX 表现出弱效力但具有高选择性。这些化合物是青光眼或涉及这两种酶的各种肿瘤的临床前评估的有趣候选者。此外，一个在硅抑制剂结合 hCA II 的研究揭示了与活性位点疏水口袋的广泛相互作用，并为这些新抑制剂的结合特性提供了分子见解。

更新日期：2020-08-03

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11