Organoruthenium Glycomimetics Exhibit High Selectivity and Nanomolar Affinity for Human Galectin-1

Area of Science:

• Biochemistry
• Chemical Biology
• Pharmacology

Background:

• Human galectin-1 (hGal-1) is an immunosuppressive lectin crucial for the tumor microenvironment.
• Developing selective hGal-1 inhibitors is challenging due to conserved galectin family binding sites.

Purpose of the Study:

• To design and synthesize potent and selective hGal-1 inhibitors.
• To characterize the inhibitory activity and selectivity of novel compounds.

Main Methods:

• Synthesis of ruthenium(II) arene complexes with modified thiodigalactoside scaffolds.
• Evaluation of inhibitor potency and selectivity against hGal-1 and hGal-3.
• Assessment of inhibitor effects on tumor cell binding, viability, and apoptosis-related markers.

Main Results:

• Developed potent nanomolar hGal-1 inhibitors with 2-3 orders of magnitude selectivity over hGal-3.
• The most potent inhibitor blocked hGal-1 binding to MDA-MB-231 tumor cells.
• Inhibitors reduced tumor cell viability and suppressed hGal-1-induced phosphatidylserine exposure in Jurkat cells.

Conclusions:

• Novel ruthenium(II) complexes represent highly selective and potent inhibitors of hGal-1.
• These compounds demonstrate therapeutic potential for targeting immunosuppressive tumor microenvironments.