Design and synthesis of novel coumarin–benzimidazole hybrids as human galectin-1 inhibitors

• Published in: Future medicinal chemistry 2024, Vol.16 (9), p.843-857
• Main Authors: Nerella, Sridhar G, Alvala, Ravi, Kalle, Arunasree M, Alvala, Mallika
• Format: Article
• Language: English
• Subjects: anticancer agents; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; coumarin–benzimidazole hybrid; Drug Design; Galectin 1 - antagonists & inhibitors; Galectin 1 - metabolism; galectin-1; Humans; MCF-7 Cells; molecular docking; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; studies
• ISSN: 1756-8919; 1756-8927; 1756-8927
• DOI: 10.4155/fmc-2023-0273

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.