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

Abstract

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.

Summary points

• GAL-1 plays a pivotal role in cancer biology and is involved in different stages of tumor progression.

• Developing non-carbohydrate-based GAL-1 inhibitors is a novel strategy to overcome the limitations like poor pharmacokinetics and target selectivity of current carbohydrate-based inhibitors.

• A simple, convenient one-step synthetic approach was adopted to synthesize both coumarin and benzimidazole derivatives having anticancer potential.

• The active candidates 6p and 6q are feasible for fluorine-18 radiolabeling to develop GAL-1-selective PET radiotracers.

Keywords: :

• anticancer agents
• coumarin–benzimidazole hybrid
• galectin-1
• in vitro studies
• molecular docking

Financial disclosure

Department of Biotechnology (DBT), Govt. of India, New Delhi, for the young investigators in cancer biology start up grants (6242-19/RGCB/PMD/DBT /MLKA/2015). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Department of Biotechnology (DBT), Govt. of India, New Delhi, for the young investigators in cancer biology start up grants (6242-19/RGCB/PMD/DBT/MLKA/2015).