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

## TL;DR

This paper introduces new ruthenium-based compounds that strongly and selectively inhibit human galectin-1, a protein linked to tumor growth and immune suppression.

## Contribution

The study presents highly selective and potent hGal-1 inhibitors with a novel organoruthenium glycomimetic scaffold.

## Key findings

- The inhibitors show nanomolar affinity and 2-3 orders of magnitude selectivity for hGal-1 over hGal-3.
- The most effective compound blocks hGal-1 binding to tumor cells and reduces cell viability.
- It also suppresses hGal-1-induced phosphatidylserine exposure in Jurkat cells.

## Abstract

Human galectin-1
(hGal-1) is an abundant β-galactoside-binding
animal lectin that plays an essential role in promoting the immunosuppressive
tumor microenvironment. Although hGal-1 has been
identified as a promising target for pharmacological inhibition, developing
potent and selective hGal-1 inhibitors has been complicated
by the high degree of sequence similarity of the glycan-binding site
across the galectin family. Herein, we present potent nanomolar hGal-1 inhibitors with unprecedented selectivity of 2 to
3 orders of magnitude over human galectin-3 (hGal-3).
Their primary structural feature is the modification of a thiodigalactoside
scaffold at the 3- and 3′-positions with a half-sandwich ruthenium­(II)
arene complex containing a bidentate 4-(2-pyridyl)-1H-1,2,3-triazol-1-yl ligand. The most potent inhibitor in the series
efficiently blocked the binding of hGal-1 to the
surface of MDA-MB-231 tumor cells, reduced their viability, and completely
suppressed hGal-1-induced phosphatidylserine exposure
in Jurkat cells, a process previously described as preaparesis rather
than classical apoptosis.