# New Chemical Scaffold with Antimicrobial Activity Identified in a Screening of Industrial Photoactive Compounds

## TL;DR

A new chemical structure was found to kill antibiotic-resistant bacteria without harming human cells, offering a promising new approach to combat antimicrobial resistance.

## Contribution

A novel chemical scaffold with antimicrobial activity was identified from industrial photoactive compounds.

## Key findings

- 4H-pyran-4-ylidenes showed dose-dependent bactericidal activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus.
- No cytotoxicity was observed in HepG2 cells at effective antimicrobial concentrations.
- Resistance to the compound was linked to point mutations in the rny locus in S. aureus.

## Abstract

Background/Objectives: The emergence of antimicrobial resistance threatens advances achieved by medicine in the last century. This situation has been exacerbated by the suboptimal outcome of screening campaigns to provide novel antimicrobials. Methods: An alternative strategy was employed to identify new chemical scaffolds with antimicrobial activity. A collection of photoactive compounds originally synthesized for industrial purposes was screened for antibacterial activity. Results: 4H-pyran-4-ylidenes were identified as active against Gram-positive bacteria. Compounds belonging to this family displayed dose-dependent bactericidal activity against both wild-type and methicillin-resistant Staphylococcus aureus. No cytotoxicity was observed in the HepG2 hepatic cell line at the concentrations required for antimicrobial activity against S. aureus. Resistance to 4H-pyran-4-ylidenes in S. aureus was associated with point mutations in the rny locus, which encodes for a ribonuclease that plays a key role in RNA homeostasis. Conclusions: These findings indicate that chemical libraries not originally intended for drug discovery can be an innovative source of chemical diversity for the development of novel antimicrobials.