# Synthesis of Phosphonate Derivatives of Benzisoselenazolones and Their Remarkable Antiureolytic Activity in Helicobacter pylori Cells

## TL;DR

This paper describes the creation of new compounds that effectively block urease activity in Helicobacter pylori, a harmful bacteria, by combining specific chemical structures.

## Contribution

The study introduces phosphonate derivatives of benzisoselenazolones with remarkable antiureolytic activity in Helicobacter pylori.

## Key findings

- Esters of the compounds showed more substantial urease inactivation than expected.
- Some compounds achieved IC50 values as low as 30–40 nM in Helicobacter pylori cells.
- The compounds were synthesized through a multistep process involving aminolysis and hydrolysis.

## Abstract

The attachment of a nickel-ion-complexing functionality
to the
structures of covalent inhibitors of ureases has been considered an
effective method for enhancing binding to these pivotal virulence
factors of various microbial pathogens. Following this approach, we
envisioned a structural combination of 1,2-benzisoselenazol-3­(2H)-one, a scaffold that produced the most significant antiureolytic
effect achieved, with a phosphonic acid group intended to block the
function of nickel ions in the catalytic mechanism. The multistep
preparation of hybrid compounds involved aminolysis of 2-(chloroseleno)­benzoyl
chloride with the key diethyl aminophosphonate intermediates, followed
by hydrolysis of the final phosphonate esters. Although not entirely
consistent with the rationale of the design idea, the esters themselves,
rather than the corresponding acids, demonstrated more substantial
inactivation of the model Sporosarcina pasteurii urease
and inhibition of ureolysis in Helicobacter pylori. In particular, IC50 values in pathogen cells reached
an unprecedented range of 30–40 nM for some compounds.