# Potent Nrf2-Inducing C6-Isothiocyanate Glucose Derivatives with Dual Antioxidant and Antitumor Activity

## TL;DR

Researchers created new glucose-based isothiocyanate compounds that show strong antioxidant and anticancer effects, with one compound standing out for its dual activity.

## Contribution

A new series of C6-ITC glucose derivatives was synthesized, showing enhanced stability and dual antioxidant/antitumor activity.

## Key findings

- Several C6-ITC derivatives activated Nrf2 at non-cytotoxic concentrations, outperforming natural ITCs.
- The compounds exhibited significant antiproliferative activity against leukemia and solid tumor cells.
- Derivative 13 showed strong Nrf2 induction and low-micromolar cytotoxicity, suggesting dual therapeutic potential.

## Abstract

Isothiocyanates (ITCs) are well-known electrophilic agents with antioxidant and anticancer properties, largely attributed to their ability to activate the Nrf2/ARE pathway. Building on previous work with C1-ITC glycosyl derivatives, we designed and synthesized a new series of S-glycosyl isothiocyanates in which the ITC group was repositioned to the C6 carbon of the glucose scaffold. This structural rearrangement yielded stable and synthetically accessible derivatives with markedly enhanced biological profiles. Several compounds showed potent Nrf2 activation at non-cytotoxic concentrations, with CD values comparable to or exceeding those of natural ITCs. In parallel, the new C6-ITC derivatives displayed significant antiproliferative activity against leukemia and solid tumor cell lines. Among them, the phenylsulfone derivative 13 emerged as a particularly promising dual-action molecule, combining strong Nrf2 induction with low-micromolar cytotoxicity. Molecular docking was used as a hypothesis-generating approach and suggested a possible interaction with the STAT3 SH2 domain, although further studies are needed to validate this target. Overall, these results support glucose-based ITCs as a versatile platform for the development of multifunctional antioxidants with complementary anticancer properties.