Small Molecules as Disinfectants and Antiseptics

Application

Anti-microbial molecules with broad spectrum activities.

Key Benefits

Effective antimicrobial scaffolds with improved broad-spectrum activities compared to current commercial disinfectants.

Market Summary

There is an increased effort in developing new antibiotics, antiseptics, and disinfectants to overcome the current resistance mechanisms. There are a number of compounds currently used for disinfectants. One class of compounds, quaternary ammonium compounds (QACs), are commonly used as disinfectants and antiseptics in clinical, household, and agricultural settings due to their ability to kill both gram-negative and gram-positive bacteria. However, a number of infections have been reported from contaminated equipment in clinical settings. Contamination by bacteria resistant to QACs can lead to infections that are often untreatable and can lead to death. As a result, researchers have also looked to similar compounds known as quaternary phosphonium compounds (QPCs). These compounds are structurally similar to QACs but contain a phosphorus heteroatom rather than nitrogen. Like QACs, QPCs work by inserting themselves into the bacterial lipid bilayer and disrupting their protective membrane, leading to death of the bacteria. Resistance to QACs often arises from either change in membrane composition and/or increase in the efflux of the compound, preventing it from being effective. Thus, there is still a need to improve antiseptic QACs and their effectiveness are focused on modifying the structures of existing compounds.

Technical Summary

Emory investigators have modified the length of the alkyl chain and the number of cationic residues in QPCs. Specifically, they found that monoQPCs with hydrocarbon tail lengths of 11-13 carbons and bisQPCs with hydrocarbon tail lengths of 8-11 carbons were effective at killing a panel of gram-negative and gram-positive bacteria. Researchers also identified one of their compounds, P6P-10,10, as a broad-spectrum antimicrobial – capable of killing both gram-positive and gram-negative bacteria with greater activity than commercial QACs including BAC (benzalkonium chloride), a disinfectant used in cleaning solutions and a preservative in shampoos, lotions, etc., CPC (cetylpyridinium chloride), an antiseptic in mouthwash and toothpaste, and 2Pyr-11,11, a potent antimicrobial. Cytotoxicity of each of the compounds was determined using a red blood cell lysis assay. This work provides an important foundation for future investigation.