# Direct synthesis of mycophenolic acid aryl esters with antioxidant and antiproliferative properties

## TL;DR

Scientists created new versions of mycophenolic acid with antioxidant and anti-cancer properties, showing promise for drug development.

## Contribution

The study introduces new MPA esters with antioxidant and immunosuppressive activity, offering potential for drug development.

## Key findings

- MPA esters with isoeugenol, methyl o-coumarate, and raspberry ketone showed high antioxidant activity.
- Selected MPA derivatives exhibited cytotoxicity and immunosuppressive effects similar to existing drugs.
- Esters with sesamol and raspberry ketone had the highest selectivity for immune cells.

## Abstract

Naturally occurring phenols were incorporated into the mycophenolic acid (MPA) core to form sixteen new MPA derivatives. Ester conjugates of MPA with isoeugenol, methyl o-coumarate, and raspberry ketone exhibited the highest antioxidant activity in the DPPH test. These derivatives were then tested against the human pancreatic cancer AsPC-1 cells, showing cytotoxicity similar to that of the referential parent compounds MPA and mycophenolate mofetil (MMF). Subsequently, most of the obtained MPA esters proved activity against the T-Jurkat cells and peripheral blood mononuclear cells (PBMCs), serving as an immunosuppressive model, and worked as inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitors. The most promising immunosuppressive conjugates were the esters of MPA with sesamol and raspberry ketone structural motifs, which held the highest selectivity index (SI) for PBMCs, thus serving as a good starting point for new drug development.

The online version contains supplementary material available at 10.1038/s41598-025-11871-5.