Design and synthesis of novel coumarin-benzimidazole hybrids as human galectin-1 inhibitors.
Nerella Sridhar GoudRavi AlvalaArunasree M KalleMallika AlvalaPublished in: Future medicinal chemistry (2024)
Aim: To develop novel non-carbohydrate inhibitors of human galectin-1 (GAL-1), we have designed a series of coumarin-benzimidazole hybrids. Methods: We synthesized and characterized the coumarin-benzimidazole hybrids and further evaluated them using an in vitro GAL-1 enzyme-linked immunosorbent assay and in silico methods. Results: Among all, the compounds 6p and 6q 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. Conclusion: Coumarin-benzimidazole hybrids can serve as potential leads to develop selective non-carbohydrate GAL-1 inhibitors for cancer therapy.
Keyphrases
- molecular docking
- fluorescent probe
- endothelial cells
- cancer therapy
- computed tomography
- induced apoptosis
- induced pluripotent stem cells
- drug delivery
- high throughput
- molecular dynamics simulations
- single cell
- pluripotent stem cells
- cell cycle arrest
- cell free
- breast cancer cells
- binding protein
- pet ct
- transcription factor
- dna binding
- case control