Synthesis and Photodecomposition Studies of Photodegradable Antibiotics and Chitin Synthase Inhibitors

The release of bioactive compounds to the biosphere, such as chitin synthase inhibitors that are causing negative effects in non-target organisms, or antibiotic agents that contribute to increasing antimicrobial resistance, has become a major problem in recent years. To try to circumvent this, the goal of this project has been to design active compounds that degrade when exposed to light. Four photodegradable scaffolds based on the core structure 1-(arylamino)-3-arylpropan-2-ol with a nitro group in different positions on the two aromatic rings were designed, and the decomposition products were investigated. The scaffolds were functionalised to give 12 target compounds that resemble commonly used chitin synthase inhibitors, and some of them displayed promising anti-lice activity (0.001-0.1 ppt). The compounds were also tested for their antimicrobial activity (6.3-50 μM), which resulted in the discovery of four active compounds. Following decomposition, all antimicrobial activity was lost and no cytotoxicity was observed, and they represent lead compounds for further development. Synthetic attempts towards several analogues of chloramphenicol were dictated by side reactions and reactivity issues, and ended up in two analogues with no antimicrobial activity. Synthesis of an analogue of the penicillin class of antibiotics was attempted and despite great efforts, problems associated with a final deprotection step was not resolved

Photodegradable Antimicrobial Agents: Synthesis and Mechanism of Degradation

As a strategy to inactivate antimicrobial agents after use, we designed a range of ethanolamine derivatives where four of them possessed interesting activity. The ethanolamine moiety facilitates photodecomposition, which in a potential drug will take place after use. Herein, the synthetic preparation of these compounds and the mechanism of photoinactivation are described.publishedVersio

Evaluation of photodegradable chitin synthetase inhibitors for the treatment of salmon lice (Lepeophtheirus salmonis)

Some photolabile ethanolamine analogues of the chitin synthetase inhibitors diflubenzuron, teflubenzuron, and lufenuron were tested for activity as anti-lice compounds towards salmon lice (Lepeophtheirus salmonis). Two teflubenzuron analogues (2 and 3) exhibited interesting biological activity whereas their corresponding photodecomposition products were inactive. One of the analogues (3) decomposes completely when irradiated at pH 8, a relevant pH for seawater. In comparison, diflubenzuron showed a 66% photodecomposition under identical conditions. Thus, ethanolamine 3 is an interesting lead compound in the search for a powerful, environmentally friendly chemical to use in salmon-lice treatment.publishedVersio

Synthesis and Photodecomposition Studies of Photodegradable Antibiotics and Chitin Synthase Inhibitors

The release of bioactive compounds to the biosphere, such as chitin synthase inhibitors that are causing negative effects in non-target organisms, or antibiotic agents that contribute to increasing antimicrobial resistance, has become a major problem in recent years. To try to circumvent this, the goal of this project has been to design active compounds that degrade when exposed to light. Four photodegradable scaffolds based on the core structure 1-(arylamino)-3-arylpropan-2-ol with a nitro group in different positions on the two aromatic rings were designed, and the decomposition products were investigated. The scaffolds were functionalised to give 12 target compounds that resemble commonly used chitin synthase inhibitors, and some of them displayed promising anti-lice activity (0.001-0.1 ppt). The compounds were also tested for their antimicrobial activity (6.3-50 μM), which resulted in the discovery of four active compounds. Following decomposition, all antimicrobial activity was lost and no cytotoxicity was observed, and they represent lead compounds for further development. Synthetic attempts towards several analogues of chloramphenicol were dictated by side reactions and reactivity issues, and ended up in two analogues with no antimicrobial activity. Synthesis of an analogue of the penicillin class of antibiotics was attempted and despite great efforts, problems associated with a final deprotection step was not resolved

Photodegradable antimicrobial agents - synthesis, photodegradation, and biological evaluation

Multi-drug resistant (MDR) bacteria are already a significant health-care problem and are making the combat of infections quite challenging. Here we report the synthesis of several new compounds containing an ethanolamine moiety, of which two exhibit promising antimicrobial activity (at the 6 μM level). All the compounds are degraded when exposed to light and form inactive products.publishedVersio

Photodegradable antimicrobial agents - synthesis, photodegradation, and biological evaluation

Multi-drug resistant (MDR) bacteria are already a significant health-care problem and are making the combat of infections quite challenging. Here we report the synthesis of several new compounds containing an ethanolamine moiety, of which two exhibit promising antimicrobial activity (at the 6 μM level). All the compounds are degraded when exposed to light and form inactive products

Photodegradable Antimicrobial Agents: Synthesis and Mechanism of Degradation

As a strategy to inactivate antimicrobial agents after use, we designed a range of ethanolamine derivatives where four of them possessed interesting activity. The ethanolamine moiety facilitates photodecomposition, which in a potential drug will take place after use. Herein, the synthetic preparation of these compounds and the mechanism of photoinactivation are described