Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, 500037, India.
G. Pulla reddy College of Pharmacy (GPRCP), Hyderabad, 500028, India.
Future Med Chem. 2024;16(9):843-857. doi: 10.4155/fmc-2023-0273. Epub 2024 Apr 12.
To develop novel non-carbohydrate inhibitors of human galectin-1 (GAL-1), we have designed a series of coumarin-benzimidazole hybrids. We synthesized and characterized the coumarin-benzimidazole hybrids and further evaluated them using an GAL-1 enzyme-linked immunosorbent assay and methods. Among all, the compounds and were found to be potent, with GAL-1 inhibition of 37.61 and 36.92%, respectively, at 10 μM in GAL-1-expressed cell culture supernatant of MCF-7 cells. These two compounds are feasible for fluorine-18 radiolabeling to develop GAL-1 selective PET radiotracers. Computational studies revealed strong binding interactions of GAL-1 with these novel coumarin-benzimidazole hybrids. Coumarin-benzimidazole hybrids can serve as potential leads to develop selective non-carbohydrate GAL-1 inhibitors for cancer therapy.
为了开发新型非碳水化合物的人半乳糖凝集素-1（GAL-1）抑制剂，我们设计了一系列香豆素-苯并咪唑杂合体。我们合成并表征了香豆素-苯并咪唑杂合体，并进一步使用 GAL-1 酶联免疫吸附测定法和方法进行了评估。在所有化合物中，化合物 和 表现出较强的抑制活性，在 MCF-7 细胞 GAL-1 表达的细胞培养上清液中，在 10 μM 时，对 GAL-1 的抑制率分别为 37.61%和 36.92%。这两种化合物都适合氟-18 放射性标记，以开发 GAL-1 选择性正电子发射断层扫描放射性示踪剂。计算研究揭示了 GAL-1 与这些新型香豆素-苯并咪唑杂合体之间的强结合相互作用。香豆素-苯并咪唑杂合体可以作为开发用于癌症治疗的选择性非碳水化合物 GAL-1 抑制剂的潜在先导化合物。
